ascorbic-acid and Cataract

Age is the biggest risk factor for cataracts, and aberrant oxidative modifications are correlated with age-related cataracts, suggesting that proper redox regulation is important for lens clarity. The lens has very high levels of antioxidants, including ascorbate and glutathione that aid in keeping the lens clear, at least in young animals and humans. We summarize current functional and genetic data supporting the hypothesis that impaired regulation of oxidative stress leads to redox dysregulation and cataract. We will focus on the essential endogenous antioxidant glutathione and the exogenous antioxidant vitamin C/ascorbate. Additionally, gene expression in response to oxidative stress is regulated in part by the transcription factor NRF2 (nuclear factor erythroid 2-related factor 2 [NFE2L2]), thus we will summarize our data regarding cataracts in

Topics: Animals; Antioxidants; Ascorbic Acid; Cataract; Glutathione; Humans; Mice; NF-E2-Related Factor 2; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Signal Transduction; Vitamins

Crystallins, the most prevalent lens proteins, have no turnover throughout the entire human lifespan. These long-lived proteins are susceptible to post-synthetic modifications, including oxidation and glycation, which are believed to be some of the primary mechanisms for age-related cataractogenesis. Thanks to high glutathione (GSH) and ascorbic acid (ASA) levels as well as low oxygen content, the human lens is able to maintain its transparency for several decades. Aging accumulates substantial changes in the human lens, including a decreased glutathione concentration, increased reactive oxygen species (ROS) formation, impaired antioxidative defense capacity, and increased redox-active metal ions, which induce glucose and ascorbic acid degradation and protein glycation. The glycated lens crystallins are either prone to UVA mediated free radical production or they attract metal ion binding, which can trigger additional protein oxidation and modification. This vicious cycle is expected to be exacerbated with older age or diabetic conditions. ASA serves as an antioxidant in the human lens under reducing conditions to protect the human lens from damage, but ASA converts to the pro-oxidative role and causes lens protein damage by ascorbylation in high oxidation or enriched redox-active metal ion conditions. This review is dedicated in honor of Dr. Frank Giblin, a great friend and superb scientist, whose pioneering and relentless work over the past 45 years has provided critical insight into lens redox regulation and glutathione homeostasis during aging and cataractogenesis.

Topics: Aging; Animals; Ascorbic Acid; Cataract; Crystallins; Glutathione; Glycosylation; Humans; Lens, Crystalline; Oxidation-Reduction; Protein Binding; Protein Processing, Post-Translational; Reactive Oxygen Species

Cataracts or clouding of the lens is the leading cause of blindness in the world. Age and diabetes are major risk factors, and with an increasing aging and diabetic population, the burden of cataracts will grow. Cataract surgery is an effective way to restore vision; however, alternatives to cataract surgery are required to reduce the looming cataract epidemic. Since it is well established that oxidative damage plays a major role in the etiology of cataracts, antioxidants have been promoted as therapies to delay and/or prevent cataracts. However, many antioxidant interventions including vitamin C have produced mixed results as anti-cataract therapies. Progress has been made towards our understanding of lens physiology and the mechanisms involved in the delivery and uptake of antioxidants to the lens which may guide future studies aimed at addressing some of the inconsistencies seen in previous animal and human studies. Of interest is the potential for vitamin C based supplements in delaying the onset of cataracts post vitrectomy which occurs in up to 80% of patients within two years. These targeted approaches are required to reduce the burden of cataract on hospitals and improve the quality of life of our aging and diabetic population.

Topics: Aging; Animals; Antioxidants; Ascorbic Acid; Cataract; Diabetes Complications; Dietary Supplements; Humans; Nutritional Physiological Phenomena; Oxidative Stress; Risk Factors; Vitrectomy; Vitreous Body

Existing studies suggest that dietary vitamins and carotenoids might be associated with a reduced risk of age-related cataract (ARC), although a quantitative summary of these associations is lacking.. The aim of this study was to conduct a meta-analysis of randomized controlled trials (RCTs) and cohort studies of dietary vitamin and carotenoid intake and ARC risk.. The MEDLINE, EMBASE, ISI Web of Science, and Cochrane Library databases were searched from inception to June 2018. The adjusted RRs and corresponding 95% CIs for the associations of interest in each study were extracted to calculate pooled estimates. Dose-response relations were assessed with the use of generalized least-squares trend estimation.. We included 8 RCTs and 12 cohort studies in the meta-analysis. Most vitamins and carotenoids were significantly associated with reduced risk of ARC in the cohort studies, including vitamin A (RR: 0.81; 95% CI: 0.71, 0.92; P = 0.001), vitamin C (RR: 0.80; 95% CI: 0.72, 0.88; P < 0.001), vitamin E (RR: 0.90; 95% CI: 0.80, 1.00; P = 0.049), β-carotene (RR: 0.90; 95% CI: 0.83, 0.99; P = 0.023), and lutein or zeaxanthin (RR: 0.81; 95% CI: 0.75, 0.89; P < 0.001). In RCTs, vitamin E (RR: 0.97; 95% CI: 0.91, 1.03; P = 0.262) or β-carotene (RR: 0.99; 95% CI: 0.92, 1.07; P = 0.820) intervention did not reduce the risk of ARC significantly compared with the placebo group. Further dose-response analysis indicated that in cohort studies the risk of ARC significantly decreased by 26% for every 10-mg/d increase in lutein or zeaxanthin intake (RR: 0.74; 95% CI: 0.67, 0.80; P < 0.001), by 18% for each 500-mg/d increase in vitamin C intake (RR: 0.82; 95% CI: 0.74, 0.91; P < 0.001), by 8% for each 5-mg/d increase in β-carotene intake (RR: 0.92; 95% CI: 0.88, 0.96; P < 0.001), and by 6% for every 5 mg/d increase in vitamin A intake (RR: 0.94; 95% CI: 0.90, 0.98; P < 0.001).. Higher consumption of certain vitamins and carotenoids was associated with a significant decreased risk of ARC in cohort studies, but evidence from RCTs is less clear.

Topics: Adult; Aged; Aged, 80 and over; Aging; Animals; Ascorbic Acid; beta Carotene; Carotenoids; Cataract; Diet; Dietary Supplements; Female; Humans; Male; MEDLINE; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Vitamin A; Vitamin E; Vitamins

Whether vitamin C is a protective factor for age-related cataract remains unclear. Thus, we conducted a meta-analysis to summarize the evidence from epidemiological studies of vitamin C and the risk of age-related cataract.. Pertinent studies were identified by searching in PubMed and in Webscience. The random effect model was used to combine the results. Meta-regression and subgroups analyses were used to explore potential sources of between-study heterogeneity. Publication bias was estimated using Egger's regression asymmetry test.. Finally, 15 articles with 20 studies for vitamin C intake and eight articles with 10 studies for serum ascorbate were included in this meta-analysis. The relative risk (RR) and 95% confidence interval of cataract for the highest versus the lowest category of vitamin C intake was 0.814 (0.707-0.938), and the associations were significant in America and Asia. Significant association of cataract risk with highest versus the lowest category of serum ascorbate was found in general [0.704 (0.564-0.879)]. Inverse associations were also found between serum ascorbate and nuclear cataract and posterior subcapsular cataract.. Higher vitamin C intake and serum ascorbate might be inversely associated with risk of cataract. Vitamin C intake should be advocated for the primary prevention of cataract.

Topics: Aging; Antioxidants; Ascorbic Acid; Cataract; Diet; Dietary Supplements; Humans; Risk Factors; Vitamins

Vision loss affects 37 million Americans older than 50 years and one in four who are older than 80 years. The U.S. Preventive Services Task Force concludes that current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in adults older than 65 years. However, family physicians play a critical role in identifying persons who are at risk of vision loss, counseling patients, and referring patients for disease-specific treatment. The conditions that cause most cases of vision loss in older patients are age-related macular degeneration, glaucoma, ocular complications of diabetes mellitus, and age-related cataracts. Vitamin supplements can delay the progression of age-related macular degeneration. Intravitreal injection of a vascular endothelial growth factor inhibitor can preserve vision in the neovascular form of macular degeneration. Medicated eye drops reduce intraocular pressure and can delay the progression of vision loss in patients with glaucoma, but adherence to treatment is poor. Laser trabeculoplasty also lowers intraocular pressure and preserves vision in patients with primary open-angle glaucoma, but long-term studies are needed to identify who is most likely to benefit from surgery. Tight glycemic control in adults with diabetes slows the progression of diabetic retinopathy, but must be balanced against the risks of hypoglycemia and death in older adults. Fenofibrate also slows progression of diabetic retinopathy. Panretinal photocoagulation is the mainstay of treatment for diabetic retinopathy, whereas vascular endothelial growth factor inhibitors slow vision loss resulting from diabetic macular edema. Preoperative testing before cataract surgery does not improve outcomes and is not recommended.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antihypertensive Agents; Ascorbic Acid; Bevacizumab; Blindness; Cataract; Cataract Extraction; Diabetic Retinopathy; Fenofibrate; Glaucoma; Humans; Hypolipidemic Agents; Intravitreal Injections; Light Coagulation; Macular Degeneration; Mass Screening; Practice Guidelines as Topic; Ranibizumab; Vision Disorders; Vision, Low; Vitamin E; Vitamins

Lens opacification or cataract reduces vision in over 80 million people worldwide and blinds 18 million. These numbers will increase dramatically as both the size of the elderly demographic and the number of those with carbohydrate metabolism-related problems increase. Preventative measures for cataract are critical because the availability of cataract surgery in much of the world is insufficient. Epidemiologic literature suggests that the risk of cataract can be diminished by diets that are optimized for vitamin C, lutein/zeaxanthin, B vitamins, omega-3 fatty acids, multivitamins, and carbohydrates: recommended levels of micronutrients are salutary. The limited data from intervention trials provide some support for observational studies with regard to nuclear - but not other types of - cataracts. Presented here are the beneficial levels of nutrients in diets or blood and the total number of participants surveyed in epidemiologic studies since a previous review in 2007.

Topics: Antioxidants; Ascorbic Acid; Cataract; Diet; Fatty Acids, Omega-3; Humans; Micronutrients; Nutritional Physiological Phenomena; Risk Factors

The major causes for cataract formation are free radicals, and these free radicals are neutralized by the presence of endogenous antioxidants in the eye. Using xenobiotics, it has been confirmed that free radicals mediate the formation of cataract. Two cataract model-selenite model and the diabetic cataract model-have been developed to study the pathophysiology of cataract formation due to free radicals and the role of antioxidants during the process of cataractogenesis. This review focuses on natural compounds with antioxidant properties that could actually be applied as an interventional strategy on a large scale and are also relatively inexpensive. A brief overview of plants with antioxidant properties that in addition possess potential anti-cataract properties has been discussed. In addition to plants, three natural compounds (curcumin, vitamin C and vitamin E), on which a lot of data exist showing anti-cataract and antioxidant activities, have also been discussed. These antioxidants can be supplemented in the diet for a better defence against free radicals. Studies on vitamin C and vitamin E have proved that they are capable of preventing lipid peroxidation, thereby preventing the generation of free radicals, but their efficacy as anti-cataract agent is questionable. Unlike vitamins C and E, curcumin is well established as an anti-cataract agent, but the issue of curcumin bioavailability is yet to be addressed. Nanotechnology proves to be a promising area in increasing the curcumin bioavailability, but still a lot more research needs to be done before the use of curcumin as an effective anti-cataract agent for humans.

Topics: Antioxidants; Ascorbic Acid; Cataract; Curcumin; Dietary Supplements; Free Radicals; Humans; Lens, Crystalline; Oxidation-Reduction; Oxidative Stress; Vitamin E

Age-related cataract is a major cause of visual impairment in the elderly. Oxidative stress has been implicated in its formation and progression. Antioxidant vitamin supplementation has been investigated in this context.. To assess the effectiveness of antioxidant vitamin supplementation in preventing and slowing the progression of age-related cataract.. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 2), MEDLINE (January 1950 to March 2012), EMBASE (January 1980 to March 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to March 2012), Open Grey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 2 March 2012. We also checked the reference lists of included studies and ongoing trials and contacted investigators to identify eligible randomized trials.. We included only randomized controlled trials in which supplementation with one or more antioxidant vitamins (beta-carotene, vitamin C and vitamin E) in any form, dosage or combination for at least one year was compared to another antioxidant vitamin or to placebo.. Two authors extracted data and assessed trial quality independently. We pooled results for the primary outcomes, i.e., incidence of cataract and incidence of cataract extraction. We did not pool results of the secondary outcomes - progression of cataract and loss of visual acuity, because of differences in definitions of outcomes and data presentation. We pooled results by type of cataract when data were available. We did not perform a sensitivity analysis.. Nine trials involving 117,272 individuals of age 35 years or older are included in this review. The trials were conducted in Australia, Finland, India, Italy, the United Kingdom and the United States, with duration of follow-up ranging from 2.1 to 12 years. The doses of antioxidant vitamins were higher than the recommended daily allowance. There was no evidence of effect of antioxidant vitamin supplementation in reducing the risk of cataract, cataract extraction, progression of cataract or in slowing the loss of visual acuity. In the pooled analyses, there was no evidence of effect of beta-carotene supplementation in reducing the risk of cataract (two trials) (relative risk (RR) 0.99, 95% confidence interval (CI) 0.91 to 1.08; n = 57,703) or in reducing the risk of cataract extraction (three trials) (RR 1.00, 95% CI 0.91 to 1.10; n = 86,836) or of vitamin E supplementation in reducing the risk of cataract (three trials) (RR 0.97, 95% CI 0.91 to 1.04; n = 50,059) or of cataract extraction (five trials) (RR 0.98, 95% CI 0.91 to 1.05; n = 83,956). The proportion of participants developing hypercarotenodermia (yellowing of skin) while on beta-carotene ranged from 7.4% to 15.8%.. There is no evidence from RCTs that supplementation with antioxidant vitamins (beta-carotene, vitamin C or vitamin E) prevents or slows the progression of age-related cataract. We do not recommend any further studies to examine the role of antioxidant vitamins beta-carotene, vitamin C and vitamin E in preventing or slowing the progression of age-related cataract. Costs and adverse effects should be weighed carefully with unproven benefits before recommending their intake above recommended daily allowances.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cataract; Disease Progression; Humans; Middle Aged; Vitamin E; Vitamins

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Asthma; Cardiovascular Diseases; Cataract; Common Cold; Humans; Nutrition Policy; Nutritional Requirements

Glucocorticoids (GC) have been widely used as a therapeutic drug for various diseases. However, there are many complications of GC therapy including cataracts. In a series of studies to elucidate the actions of GC using 15-day-old developing chick embryos, we found that GC produced hyperglycemia, hyperlipemia, osteoporosis, and cataractous lenses with a high incidence (>90%) within 48 h. Cataract formation is caused by oxidative stresses, probably derived from GC effects on the main target organ, the liver, and can be prevented by radical scavengers including ascorbic acid, and insulin. Ascorbic acid does not inhibit the inflammatory and immunosuppressive effects of GC. Therefore by analyzing and decreasing risk factors producing side effects, it will be possible to improve GC therapy without the loss of GC activity.

Topics: Animals; Ascorbic Acid; Cataract; Chick Embryo; Disease Models, Animal; Free Radical Scavengers; Glucocorticoids; Glutathione; Insulin; Lipid Peroxides; Liver; Mifepristone; Oxidative Stress; Phosphoprotein Phosphatases; Receptors, Glucocorticoid

FREE RADICALS AND THE THEORY OF AGING: Severe oxidative stress progressively leads to cell dysfunction and ultimately cell death. Oxidative stress is defined as an imbalance between pro-oxidants and/or free radicals on the one hand, and anti-oxidizing systems on the other. The oxygen required for living may indirectly be responsible for negative effects; these deleterious effects are due to the production of free radicals, which are toxic for the cells (superoxide anions, hydroxyl radicals, peroxyl radicals, hydrogen peroxide, hydroperoxides and peroxinitrite anions). Free radical attacks are responsible for cell damage and the targeted cells are represented by the cell membranes, which are particularly rich in unsaturated fatty acids, sensitive to oxidation reactions; DNA is also the target of severe attacks by these reactive oxygen species (ROS).. These are represented by the enzymes and free radical captors. The latter are readily oxidizable composites. The free radical captor or neutralization systems of these ROS use a collection of mechanisms, vitamins (E and C), enzymes [superoxide dismutase (SOD), glutathion peroxidase (GPx) and others], and glutathion reductase (GSH), capable of neutralizing peroxinitrite. The efficacy of this system is dependent on the genome for the enzymatic defence systems, and on nutrition for the vitamins. Some strategies aimed at reducing oxidative stress-related alterations have been performed in animals. However, only a few can be used and are efficient in humans, such as avoidance of unfavourable environmental conditions (radiation, dietary carcinogens, smoking...) and antioxidant dietary supplementation.. Epidemiological data suggest that antioxidants may have a beneficial effect on many age-related diseases: atherosclerosis, cancer, some neurodegenerative and ocular diseases. However, the widespread use of supplements is hampered by several factors: the lack of prospective and controlled studies; insufficient knowledge on the pro-oxidant, oxidant and ant-oxidant properties of the various supplements; growing evidence that free radicals are not only by-products, but also play an important role in cell signal transduction, apoptosis and infection control.. Although current data indicate that antioxidants cannot prolong maximal life span, the beneficial impact of antioxidants on various age-related degenerative diseases may forecast an improvement in life span and enhance quality of life. The current lack of sufficient data does not permit the systematic recommendation of anti-oxidants. Nevertheless, antioxidant-rich diets with fruit and vegetables should be recommended.

Topics: Aging; Alzheimer Disease; Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Carotenoids; Cataract; Chronic Disease; Disease Models, Animal; Evidence-Based Medicine; Free Radicals; Humans; Lutein; Macular Degeneration; Neoplasms; Oxidative Stress; Parkinson Disease; Reactive Oxygen Species; Vitamin E

Topics: Aged; Aging; Antioxidants; Ascorbic Acid; Carotenoids; Cataract; Geriatric Assessment; Humans; Nutrition Assessment; Nutritional Status; Oxidative Stress; Prevalence; Risk Factors; Vitamin E

Oxidation is a biochemical process of loss of electrons associated with another of reception called reduction. This process is capital for life, because it takes part in the production of cellular energy. Oxidative stress appears when oxidation is excessive. This reality is complex in all biological levels, and cannot be measured or defined by a single parameter. A great number of diseases have been related to oxidative stress and generation of free radicals. For this reason, antioxidant therapies and diets (such as mediterranean diet) rich or enriched with antioxidants seem to prevent or at least to attenuate the organic deterioration originated by an excessive oxidative stress.

Topics: Acute Kidney Injury; Aged; Aging; Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Cataract; Diabetes Mellitus; Diet; Humans; Hypertension; Liver Diseases; Neoplasms; Oxidation-Reduction; Oxidative Stress; Primary Prevention; Risk Factors; Selenium; Vitamin E

It is clear that oxidative stress is associated with compromises to the lens. Recent literature indicates that antioxidants may ameliorate that risk and may actually decrease risk for cataract. This article will briefly review the etiology of cataract. It will also review the epidemiologic information with emphasis on roles for vitamins C and E and carotenoids. More thorough recent reviews are available.

Topics: Aging; Animals; Antioxidants; Ascorbic Acid; Carotenoids; Cataract; Dietary Supplements; Humans; Incidence; Oxidative Stress; Prevalence; Risk Factors; Sunlight; Vitamin E

To assess the balance of benefits and risks of supplementation with beta-carotene, vitamin E, vitamin C, and multivitamins on cancer, cardiovascular (CVD), and eye diseases.. Physicians' Health Study II (PHS II) is a randomized, double-blind, placebo-controlled trial enrolling 15,000 willing and eligible physicians aged 55 years and older. PHS II will utilize a 2 x 2 x 2 x 2 factorial design to test alternate day beta-carotene, alternate day vitamin E, daily vitamin C, and a daily multivitamin, in the prevention of total and prostate cancer, CVD, and the age-related eye diseases, cataract and macular degeneration. PRIOR RESULTS: The final results of the recently completed Physicians' Health Study I (PHS I), a randomized, double-blind, placebo-controlled trial in 22,071 healthy US male physicians, indicated that beta-carotene supplementation (50 mg on alternate days) had no significant benefit or harm on cancer or CVD during more than 12 years of treatment and follow-up. In regards to cancer, there were possible benefits on total and prostate cancer in those with low baseline levels assigned to beta-carotene, a finding compatible with the Chinese Cancer Prevention Study for combined treatment with beta-carotene, vitamin E, and selenium in a poorly nourished population. Further, with respect to CVD, there were apparent benefits of beta-carotene supplementation on subsequent vascular events among a small subgroup of 333 men with prior angina or revascularization. The currently available data from randomized trials of primary prevention are sparse and inconsistent for vitamin E and non-existent for vitamin C and multivitamins. For eye diseases, namely cataract and age-related macular degeneration, there are no completed large-scale randomized trials of antioxidant vitamins.. PHS II is unique in several respects. PHS II is the only primary prevention trial in apparently healthy men testing the balance of benefits and risks of vitamin E on cancer and CVD. In addition, PHS II is the only primary prevention trial in apparently healthy men to test the balance of benefits and risks of vitamin C, multivitamins, as well as any single antioxidant vitamin, alone and in combination, on cancer, CVD, and eye diseases. Finally, PHS II is the only trial testing a priori the hypotheses that beta-carotene and vitamin E may reduce the risks of prostate cancer. Thus, PHS II will add unique as well as importantly relevant and complementary information to the totality of evidence from other completed and ongoing large-scale randomized trials on the balance of benefits and risks of beta-carotene, vitamin E, vitamin C, and multivitamins alone and in combination on prevention of cancer, CVD and eye diseases.

Topics: Aged; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Cataract; Double-Blind Method; Female; Follow-Up Studies; Humans; Macular Degeneration; Male; Middle Aged; Neoplasms; Sample Size; Vitamin E

Topics: Animals; Antioxidants; Ascorbic Acid; Cataract; Drug Therapy, Combination; Humans; Lens, Crystalline; Oxidative Stress; Risk Factors; Vitamin E

The current recommended dietary allowance (RDA) for vitamin C for adult nonsmoking men and women is 60 mg/d, which is based on a mean requirement of 46 mg/d to prevent the deficiency disease scurvy. However, recent scientific evidence indicates that an increased intake of vitamin C is associated with a reduced risk of chronic diseases such as cancer, cardiovascular disease, and cataract, probably through antioxidant mechanisms. It is likely that the amount of vitamin C required to prevent scurvy is not sufficient to optimally protect against these diseases. Because the RDA is defined as "the average daily dietary intake level that is sufficient to meet the nutrient requirement of nearly all healthy individuals in a group," it is appropriate to reevaluate the RDA for vitamin C. Therefore, we reviewed the biochemical, clinical, and epidemiologic evidence to date for a role of vitamin C in chronic disease prevention. The totality of the reviewed data suggests that an intake of 90-100 mg vitamin C/d is required for optimum reduction of chronic disease risk in nonsmoking men and women. This amount is about twice the amount on which the current RDA for vitamin C is based, suggesting a new RDA of 120 mg vitamin C/d.

Topics: Adult; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Cataract; Clinical Trials as Topic; Female; Humans; Lipid Peroxidation; Male; Neoplasms; Nutrition Policy; Scurvy

Age-related cataract and age-related macular degeneration (AMD) are important public health problems. Approximately 50% of the 30 to 50 million cases of blindness worldwide result from unoperated cataract. In the US and other developed countries AMD is the leading cause of blindness, but age-related cataract remains the leading cause of visual disability. Age-related cataract and AMD represent an enormous economic burden. In the United States more than 1.3 million cataract extractions are performed annually at a cost of approximately $3.5 billion. Much of the experimental research on the etiology of cataract and AMD has focused on the role of nutritional antioxidants (vitamin C, vitamin E, and carotenoids). Evidence from epidemiologic studies support a role for nutritional antioxidants in delaying the onset of these age-related vision disorders. Although it is not yet possible to conclude that antioxidant nutrients have a role in prevention of cataract or AMD, a summary of the epidemiologic evidence suggests that it is prudent to consume diets high in vitamins C and E and carotenoids, particularly the xanthophylls, as insurance against the development of cataract and AMD.

Topics: Antioxidants; Ascorbic Acid; Carotenoids; Cataract; Dietary Supplements; Humans; Macular Degeneration; Riboflavin; Vitamin E; Vitamins

While many experimental studies have shown a protective effect of vitamin C in age-related cataract, other studies have revealed contrasting roles for this nutrient. Oxidative damage in the lens can be prevented by vitamin C. However, a pro-oxidant effect of vitamin C through H2O2 generation has been suggested. Vitamin C has also been shown to play a role in protein glycation, which is observed in cataract formation. A protective effect of dietary energy restriction appears to be inversely related to plasma vitamin C levels in rodents. Moreover, conclusions from human epidemiological and intervention studies are not uniform. The available evidence suggests that maintenance of sufficient plasma vitamin C is needed to prevent oxidative damage in the lens. More research will be needed in order to confirm the relative importance of of the different roles of vitamin C in the eye lens.

Topics: Aging; Animals; Antioxidants; Ascorbic Acid; Cataract; Humans; Hydrogen Peroxide; Oxidants; Oxidative Stress

In this review the role of UVB/290-320 nm/ and visible light radiation in generating of free radicals in the lens is described, which is the main factor leading to development of senile cataract. Also the mechanisms of antioxidant defence are presented especially glutathione and ascorbic acid. We review the literature connected with diet supplementation of antioxidants /vit. E, C, selenium/. According to actual theories the use of sun-glasses with UVB-filters, and antioxidant diet supplementation seems to be useful in prevention of age-related cataract.

Topics: Ascorbic Acid; Cataract; Eyeglasses; Food, Fortified; Free Radicals; Glutathione; Humans; Lens, Crystalline; Ultraviolet Rays

The recent scientific literature indicates that beyond merely protecting against scurvy vitamin C contributes to many aspects of human health. The main areas of research reviewed include: 1. Vitamin C requirements of smokers. The data indicate that the vitamin C requirement of smokers is higher by at least 60 mg per day (up to 140 mg per day) than that of nonsmokers. 2. Important functions of the body, such as immune response, pulmonary function, and iron absorption are related to vitamin C intakes. Daily vitamin C intake of at least 150-200 mg per day enhance these functions. 3. Vitamin C may play critical roles in the prevention of CHD, cancer and cataract. Based on the available data, vitamin C intakes of at least 80-120 mg per day are associated with lowering the risk of these chronic diseases. 4. The literature documents that these and much higher intake levels of vitamin C are safe.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Cataract; Diet; Health Status; Humans; Neoplasms; Nutrition Policy; Nutritional Requirements

Light and oxygen are necessary for the function of the eye. However, when present in excess or in uncontrolled circumstances, they appear to be related, probably causally, to the development of cataract. Compromises of function of the lens and retina with aging are exacerbated by depleted or diminished primary antioxidant reserves, antioxidant enzyme capabilities, and diminished secondary defenses such as proteases. Smoking appears to provide an additional oxidative challenge associated with depletion of antioxidants as well as with enhanced risk for cataract formation. Poor education and lower socioeconomic status are associated with poorer nutriture and are also significantly related to increased risk for these debilities. Optimizing nutriture, including diets rich in fruit and vegetables, may provide the least costly and most practicable means to delay cataract.

Topics: Aging; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Cataract; Clinical Trials as Topic; Humans; Oxidation-Reduction; Public Health; Vitamin E

Senile cataract indicates the opacity of ocular lenses occurring in old and especially in very old people. Lens proteins are extremely long-living and often show oxidative damages. Aging and smoking appear to be the greatest risk factors for the development of lens opacities. The sufficient antioxidant protection of young lenses decreases with the aging process. Consequently, the importance of other protective factors increases. Nutritional factors, particularly vitamins with antioxidant properties, may influence the development of senile cataracts in the ocular lens. Meanwhile an association between the supply with vitamin C, E and beta-carotene and the risk of cataract development was demonstrated in animal studies and also in an increasing number of epidemiological studies. These epidemiological studies mainly support the hypothesis that higher vitamin intakes reduce the risk of developing cataracts in old age. The antioxidant properties of the named nutrients give a plausible explanation for the mechanism of cataractogenesis. On the basis of the present data definitive recommendation, necessary for cataract prevention can not yet be established. Some results seem to support higher recommendations. At the moment several large human intervention trials are carried out. Form these studies a further confirmation of the antioxidant hypothesis and of a dose-response-relationship are expected.

Topics: Adult; Aged; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; beta Carotene; Carotenoids; Cataract; Child; Humans; Risk Factors; Vitamin E; Vitamin E Deficiency

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cadmium; Cataract; Humans; Lens, Crystalline; Risk Factors; Smoking

A comprehensive review of the literature indicates that populations with long-term consumption of higher than RDA levels of vitamin C (> or = 60 mg/day) from foods and/or supplements have reduced risks of cancer at several sites, cardiovascular disease, and cataracts. The safety of higher than RDA intakes of vitamin C is confirmed in eight placebo-controlled, double-blind studies and six non-placebo clinical trials in which up to 10,000 mg of vitamin C was consumed daily for up to 3 years. There are no clinical data which suggest that vitamin C's enhancement of non-heme iron absorption in individuals with low iron status could be a critical factor in the possible increased risk of heterozygous hemochromatosis-related cardiovascular disease. In fact, the cumulative data do not confirm that iron status is related to risk of cardiovascular disease. Moreover, higher than RDA intakes of vitamin C have been associated with several indices of lowered cardiovascular disease risk including increases in HDL, and decreases in LDL oxidation, blood pressure and cardiovascular mortality.

Topics: Ascorbic Acid; Cardiovascular Diseases; Cataract; Female; Humans; Iron; Iron Deficiencies; Male; Neoplasms

Topics: Antioxidants; Ascorbic Acid; Cataract; Humans; Randomized Controlled Trials as Topic; Vitamin E

Despite a realisation that antioxidants will not delay ageing in healthy older people, there is increasing scientific interest in the role of free radical oxidants in a number of diseases associated with older age. For most of these diseases there is suggestive theoretical and laboratory evidence but not confirmatory clinical evidence. Free radical damage seems likely to be significant in the pathophysiology of atherosclerosis, ischaemia-reperfusion injury, Parkinson's disease, cataract, some cancers and rheumatoid arthritis. Evidence to suggest a protective effect from antioxidant vitamins exists for ischaemic heart disease, cataract and some cancers. Attempts to influence the outcome of other diseases such as ischaemia-reperfusion injury, Parkinson's disease and rheumatoid arthritis have so far failed to achieve positive results. Research interest in the field is increasing although hampered by methodological difficulties and the limited financial return for drug companies. In the meantime there seems no reason to discourage older people who wish to ingest extra vitamin E and vitamin C. A diet with adequate vegetables and fruits should provide sufficient beta carotene.

Topics: Aged; Aging; Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Cataract; Diet; Free Radicals; Humans; Parkinson Disease; Reactive Oxygen Species; Reperfusion Injury; Vitamin A; Vitamin E

Cataract is one of the major causes of age-dependent visual impairment and blindness. The geographic distribution of cataract is known to be associated with the intensity and duration of sunlight--especially of the ultraviolet frequency--at particular places. Exposure of animals and humans to oxygen has also been known to result in cataract formation. Studies described in this communication indicate that the ocular lens is physiologically damaged when exposed to an environment of active species of oxygen, commonly referred to as oxyradicals. Several photochemical and nonphotochemical models have been described. The results suggest that an intraocular generation of active oxygen may constitute a significant risk factor in the overall pathogenesis of senile cataracts. The cataractogenic effect of oxyradicals, however, can be thwarted by nutritional and metabolic antioxidants such as ascorbate, vitamin E, and pyruvate. These agents, therefore, may be useful for prophylaxis or therapy against cataracts.

Topics: Animals; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Cataract; Humans; Lipid Metabolism; Oxygen; Polysorbates; Pyruvates; Pyruvic Acid; Sunlight; Vitamin E

The ocular lens, which is continually exposed to light and ambient oxygen, is at high risk of photooxidative damage resulting in cataract. Oxygen free radicals appear to impair not only lens crystallins which will aggregate and precipitate forming opacities but also proteolytic enzymes whose function it would be to eliminate the damaged proteins. Apart from an enzymatic defense system consisting of superoxide dismutase, catalase and glutathione peroxidase against excited oxygen species the lens contains the antioxidant vitamins C, E and presumably beta-carotene as another line of defense. In vitro and in vivo studies in different animal species have demonstrated a significant protective effect of vitamins C and E against light-induced cataract. Sugar and steroid cataracts were prevented as well. Epidemiological evidence in humans suggests that persons with comparatively higher intakes or blood concentrations of antioxidant vitamins are at a reduced risk of cataract development. These positive findings established by several research groups justify extensive intervention trials with antioxidant vitamins in humans using presenile cataract development as a model.

Topics: Age Factors; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Cataract; Drug Therapy, Combination; Humans; Oxidation-Reduction; Risk Factors; Vitamin E

Topics: Animals; Ascorbic Acid; Cataract; Cell Membrane; Eye; Glutathione; Humans; Hydrogen Peroxide; Hydroxides; Hydroxyl Radical; Lens, Crystalline; Light; NADP; Oxidation-Reduction; Photochemistry; Superoxides; Vitamin E

Topics: Animals; Aqueous Humor; Ascorbic Acid; Cataract; Cattle; Eye; Humans; Intraocular Pressure; Lens, Crystalline; Mannitol; Ocular Physiological Phenomena; Oxidation-Reduction; Radiation Effects; Ultraviolet Rays

Topics: Animals; Anterior Chamber; Aqueous Humor; Ascorbic Acid; Blood Pressure; Cataract; Child; Cryosurgery; Diabetes Complications; Glaucoma; Gonioscopy; Humans; Intraocular Pressure; Microsurgery; Miotics; Ophthalmodynamometry; Sclera; Thrombosis; Tonometry, Ocular; Uveitis, Anterior; Visual Field Tests

To test whether supplementation with alternate-day vitamin E or daily vitamin C affects the incidence of age-related cataract in a large cohort of men.. In a randomized, double-masked, placebo-controlled trial, 11,545 apparently healthy US male physicians 50 years or older without a diagnosis of cataract at baseline were randomly assigned to receive 400 IU of vitamin E or placebo on alternate days and 500 mg of vitamin C or placebo daily.. Incident cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-report confirmed by medical record review.. Long-term use of vitamin E and C supplements has no appreciable effect on cataract.. After 8 years of treatment and follow-up, 1174 incident cataracts were confirmed. There were 579 cataracts in the vitamin E-treated group and 595 in the vitamin E placebo group (hazard ratio, 0.99; 95% confidence interval, 0.88-1.11). For vitamin C, there were 593 cataracts in the treated group and 581 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.91-1.14).. Long-term alternate-day use of 400 IU of vitamin E and daily use of 500 mg of vitamin C had no notable beneficial or harmful effect on the risk of cataract.. clinicaltrials.gov Identifier: NCT00270647.

Topics: Aged; Aging; Antioxidants; Ascorbic Acid; Cataract; Cataract Extraction; Double-Blind Method; Drug Combinations; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Physicians; Risk Assessment; United States; Visual Acuity; Vitamin E

To determine if antioxidant supplements (beta carotene and vitamins C and E) can decrease the progression of cataract in rural South India.. The Antioxidants in Prevention of Cataracts (APC) Study was a 5 year, randomised, triple masked, placebo controlled, field based clinical trial to assess the ability of interventional antioxidant supplements to slow cataract progression. The primary outcome variable was change in nuclear opalescence over time. Secondary outcome variables were cortical and posterior subcapsular opacities and nuclear colour changes; best corrected visual acuity change; myopic shift; and failure of treatment. Annual examinations were performed for each subject by three examiners, in a masked fashion. Multivariate modelling using a general estimating equation was used for analysis of results, correcting for multiple measurements over time.. Initial enrolment was 798 subjects. Treatment groups were comparable at baseline. There was high compliance with follow up and study medications. There was progression in cataracts. There was no significant difference between placebo and active treatment groups for either the primary or secondary outcome variables.. Antioxidant supplementation with beta carotene, vitamins C and E did not affect cataract progression in a population with a high prevalence of cataract whose diet is generally deficient in antioxidants.

Topics: Adult; Antioxidants; Ascorbic Acid; Cataract; Cataract Extraction; Developing Countries; Dietary Supplements; Double-Blind Method; Humans; India; Middle Aged; Multivariate Analysis; Prospective Studies; Treatment Failure; Visual Acuity; Vitamin E; Vitamins

To investigate the association at baseline between plasma levels of selected vitamins and the presence and type of cataract in the participants in The Italian-American Trial of Nutritional Supplements and Age-related Cataract.. At baseline, the participants (1020, 710 with "early cataract" and 310 with "no cataract," 55-75 years of age) received an ocular examination, photographic lens grading, and measurement of plasma levels of vitamins A, C, E, beta-carotene, and of red blood cell glutathione reductase activity.. In multiple logistic models adjusted for potential confounders, high vitamin C levels were associated with a protective effect on nuclear (N) [OR: 0.54; 95% CI: 0.30, 0.97] and posterior subcapsular (PSC) cataract (OR: 0.37; 95% CI: 0.15, 0.93). High vitamin E levels were associated with increased prevalence of cortical cataract (C) (OR: 1.99; 95% CI: 1.02-3.90), PSC (OR: 3.27; 95% CI: 1.34, 7.96) and of any cataract (OR: 1.86; 95% CI: 1.08, 3.18).. In agreement with some earlier studies, we found higher plasma levels of vitamin C to be associated with reduced prevalence of N and PSC cataracts. The finding of an increased prevalence of some types of cataract with higher levels of vitamin E was unexpected, has not been previously reported, and could be due to unadjusted confounding.

Topics: Aged; Aging; Ascorbic Acid; beta Carotene; Cataract; Chromatography, High Pressure Liquid; Dietary Supplements; Erythrocyte Membrane; Female; Glutathione Reductase; Humans; Italy; Male; Middle Aged; Prevalence; Quality Control; United States; Vitamin A; Vitamin E

To assess the association of ocular disorders and high doses of antioxidants or zinc with mortality in the Age-Related Eye Disease Study (AREDS).. Baseline fundus and lens photographs were used to grade the macular and lens status of AREDS participants. Participants were randomly assigned to receive oral supplements of high-dose antioxidants, zinc, antioxidants plus zinc, or placebo. Risk of all-cause and cause-specific mortality was assessed using adjusted Cox proportional hazards models.. During median follow-up of 6.5 years, 534 (11%) of 4753 AREDS participants died. In fully adjusted models, participants with advanced age-related macular degeneration (AMD) compared with participants with few, if any, drusen had increased mortality (relative risk [RR], 1.41; 95% confidence interval [CI], 1.08-1.86). Advanced AMD was associated with cardiovascular deaths. Compared with participants having good acuity in both eyes, those with visual acuity worse than 20/40 in 1 eye had increased mortality (RR, 1.36; 95% CI, 1.12-1.65). Nuclear opacity (RR, 1.40; 95% CI, 1.12-1.75) and cataract surgery (RR, 1.55; 95% CI, 1.18-2.05) were associated with increased all-cause mortality and with cancer deaths. Participants randomly assigned to receive zinc had lower mortality than those not taking zinc (RR, 0.73; 95% CI, 0.61-0.89).. The decreased survival of AREDS participants with AMD and cataract suggests that these conditions may reflect systemic rather than only local processes. The improved survival in individuals randomly assigned to receive zinc requires further study.

Topics: Aged; Aged, 80 and over; Aging; Antioxidants; Ascorbic Acid; beta Carotene; Cataract; Cataract Extraction; Cause of Death; Drug Therapy, Combination; Female; Humans; Macular Degeneration; Male; Middle Aged; Proportional Hazards Models; Survival Rate; United States; Vision Disorders; Visually Impaired Persons; Vitamin E; Zinc Oxide

Funding surgery worldwide for age-related cataract (ARC), a leading cause of blindness, is a huge economic burden. Non-surgical means of slowing ARC progression could benefit patients and reduce this burden.. To determine if a mixture of oral antioxidant micronutrients [mg/day] (beta-carotene [18], vitamin C [750], and vitamin E [600]) would modify progression of ARC.. REACT was a multi-centered, prospective, double-masked, randomized, placebo-controlled, 3-year trial.. Consecutive adult American and English outpatients with early ARC were recruited.. Four-hundred-and-forty-five patients were eligible; 297 were randomized; 231 (78%) were followed for two years; 158 (53%) were followed for three years; 36 (12%) were followed for four years. Twelve patients died during the trial (9 on vitamins; 3 on placebo (p = 0.07)). There were no serious safety issues.. After a three-month placebo run-in, patients were randomized by clinical center to the vitamin or placebo groups and followed every four months.. Cataract severity was documented with serial digital retroillumination imagery of the lens; progression was quantified by image analysis assessing increased area of opacity. This measure of area, 'increase % pixels opaque' (IPO), was the main outcome measure.. There were no statistically significant differences between the treatment groups at baseline. The characteristics of dropouts and the mean follow-up times by treatment group were the same. After two years of treatment, there was a small positive treatment effect in U.S. patients (p = 0.0001); after three years a positive effect was apparent (p = 0.048) in both the U.S. and the U.K. groups. The positive effect in the U.S. group was even greater after three years: (IPO = 0.389 (vitamin) vs. IPO = 2.517 (placebo); p = 0.0001). There was no statistically significant benefit of treatment in the U.K. group. In spite of nearly perfect randomization into treatment groups, the U.S. and U.K. cohorts differed significantly.. Daily use of the afore-mentioned micronutrients for three years produced a small deceleration in progression of ARC.

Topics: Administration, Oral; Aged; Aging; Antioxidants; Ascorbic Acid; beta Carotene; Cataract; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Micronutrients; Prospective Studies; United Kingdom; United States; Vitamin E

Experimental and observational data suggest that micronutrients with antioxidant capabilities may retard the development of age-related cataract.. To evaluate the effect of a high-dose antioxidant formulation on the development and progression of age-related lens opacities and visual acuity loss.. The 11-center Age-Related Eye Disease Study (AREDS) was a double-masked clinical trial. Participants were randomly assigned to receive daily oral tablets containing either antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg) or no antioxidants. Participants with more than a few small drusen were also randomly assigned to receive tablets with or without zinc (80 mg of zinc as zinc oxide) and copper (2 mg of copper as cupric oxide) as part of the age-related macular degeneration trial. Baseline and annual (starting at year 2) lens photographs were graded at a reading center for the severity of lens opacities using the AREDS cataract grading scale.. Primary outcomes were (1) an increase from baseline in nuclear, cortical, or posterior subcapsular opacity grades or cataract surgery, and (2) at least moderate visual acuity loss from baseline (>/=15 letters). Primary analyses used repeated-measures logistic regression with a statistical significance level of P =.01. Serum level measurements, medical histories, and mortality rates were used for safety monitoring.. Of 4757 participants enrolled, 4629 who were aged from 55 to 80 years had at least 1 natural lens present and were followed up for an average of 6.3 years. No statistically significant effect of the antioxidant formulation was seen on the development or progression of age-related lens opacities (odds ratio = 0.97, P =.55). There was also no statistically significant effect of treatment in reducing the risk of progression for any of the 3 lens opacity types or for cataract surgery. For the 1117 participants with no age-related macular degeneration at baseline, no statistically significant difference was noted between treatment groups for at least moderate visual acuity loss. No statistically significant serious adverse effect was associated with treatment.. Use of a high-dose formulation of vitamin C, vitamin E, and beta carotene in a relatively well-nourished older adult cohort had no apparent effect on the 7-year risk of development or progression of age-related lens opacities or visual acuity loss.

Topics: Aged; Aged, 80 and over; Aging; Antioxidants; Ascorbic Acid; beta Carotene; Cataract; Dietary Supplements; Disease Progression; Double-Blind Method; Female; Humans; Lens, Crystalline; Male; Middle Aged; Odds Ratio; Photography; Prospective Studies; Risk Factors; Vision Disorders; Visual Acuity; Vitamin E

To assess the balance of benefits and risks of supplementation with beta-carotene, vitamin E, vitamin C, and multivitamins on cancer, cardiovascular (CVD), and eye diseases.. Physicians' Health Study II (PHS II) is a randomized, double-blind, placebo-controlled trial enrolling 15,000 willing and eligible physicians aged 55 years and older. PHS II will utilize a 2 x 2 x 2 x 2 factorial design to test alternate day beta-carotene, alternate day vitamin E, daily vitamin C, and a daily multivitamin, in the prevention of total and prostate cancer, CVD, and the age-related eye diseases, cataract and macular degeneration. PRIOR RESULTS: The final results of the recently completed Physicians' Health Study I (PHS I), a randomized, double-blind, placebo-controlled trial in 22,071 healthy US male physicians, indicated that beta-carotene supplementation (50 mg on alternate days) had no significant benefit or harm on cancer or CVD during more than 12 years of treatment and follow-up. In regards to cancer, there were possible benefits on total and prostate cancer in those with low baseline levels assigned to beta-carotene, a finding compatible with the Chinese Cancer Prevention Study for combined treatment with beta-carotene, vitamin E, and selenium in a poorly nourished population. Further, with respect to CVD, there were apparent benefits of beta-carotene supplementation on subsequent vascular events among a small subgroup of 333 men with prior angina or revascularization. The currently available data from randomized trials of primary prevention are sparse and inconsistent for vitamin E and non-existent for vitamin C and multivitamins. For eye diseases, namely cataract and age-related macular degeneration, there are no completed large-scale randomized trials of antioxidant vitamins.. PHS II is unique in several respects. PHS II is the only primary prevention trial in apparently healthy men testing the balance of benefits and risks of vitamin E on cancer and CVD. In addition, PHS II is the only primary prevention trial in apparently healthy men to test the balance of benefits and risks of vitamin C, multivitamins, as well as any single antioxidant vitamin, alone and in combination, on cancer, CVD, and eye diseases. Finally, PHS II is the only trial testing a priori the hypotheses that beta-carotene and vitamin E may reduce the risks of prostate cancer. Thus, PHS II will add unique as well as importantly relevant and complementary information to the totality of evidence from other completed and ongoing large-scale randomized trials on the balance of benefits and risks of beta-carotene, vitamin E, vitamin C, and multivitamins alone and in combination on prevention of cancer, CVD and eye diseases.

Topics: Aged; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Cataract; Double-Blind Method; Female; Follow-Up Studies; Humans; Macular Degeneration; Male; Middle Aged; Neoplasms; Sample Size; Vitamin E

The Age-Related Eye Disease Study (AREDS) was initially conceived as a long-term multicenter, prospective study of the clinical course of age-related macular degeneration (AMD) and age-related cataract. Data on progression rates and risk factors from the study will increase understanding of the clinical course of both conditions, generate hypotheses about etiology, and aid in the design of clinical trials of potential interventions. In addition to collecting natural history data, AREDS includes a clinical trial of high-dose vitamin and mineral supplements for AMD and a clinical trial of high-dose vitamin supplements for cataract. The clinical trials were initiated largely because of the widespread public use in the United States of commercially available pharmacologic doses of vitamins and minerals to treat these two eye conditions and the absence of definitive studies on the safety and efficacy of their use. Important design issues for the clinical trials include: defining cataract and AMD, estimating event rates, determining the type and dosage of vitamins and minerals to be tested for each condition, and identifying the parameters necessary for monitoring safety and efficacy. This paper describes the AREDS design, including the study rationale and operational structure, and the approach adopted to combine, for two diseases, clinical trials with a natural history study.

Topics: Aged; Aged, 80 and over; Aging; Antioxidants; Ascorbic Acid; Cataract; Disease Progression; Drug Monitoring; Follow-Up Studies; Humans; Longitudinal Studies; Macular Degeneration; Middle Aged; Placebos; Prospective Studies; Research Design; Risk Factors; Safety; Vitamin E; Zinc

The quantitation of tocopherols and carotenoids in lipid extracts of cataractous human lenses was performed in parallel with those of matched samples of plasma, which was also analysed at the same time. Alpha-tocopherol in cataractous lenses from elderly human subjects was present at 4.4 mumoles/kg wet weight, much less than the mean of 33 mumoles/l in plasma from these subjects. The mean ratio of alpha- and gamma-tocopherols was 3.5 in the lenses, and 11.3 in plasma. Lens extracts contained no detectable alpha- or beta-carotene, lycopene, or beta-cryptoxanthin. However, all the lens extracts contained a pigment with the retention time and spectrum of lutein and zeaxanthin. Using the molar extinction coefficient of lutein this was present at ca. 0.03 microM, compared with 0.2 microM in plasma. Seven patients with bilateral cataracts had one of their cataractous lenses removed and analysed, and were then given either an oral placebo, or an oral supplement of ascorbate, alpha-tocopherol and beta-carotene. Three months later, the second cataractous lens, and a blood sample, were analysed. Three of the seven had received the active supplement, as confirmed by substantially raised blood levels of alpha-tocopherol and beta-carotene, and raised aqueous humour levels of vitamin C. However, lens tocopherol levels remained unchanged, and no beta-carotene could be detected in the lenses after supplementation. This preliminary evidence needs to be confirmed in larger studies.

Topics: Aged; Ascorbic Acid; beta Carotene; Carotenoids; Cataract; Diet; Female; Humans; Lens, Crystalline; Male; Regression Analysis; Vitamin E

Topics: Amino Acids; Ascorbic Acid; Cataract; Clinical Trials as Topic; Densitometry; Drug Combinations; Humans; Inositol; Lens Cortex, Crystalline; Pyridoxine

This paper begins with a discussion and explanation of the special features and requirements of a controlled clinical trial of the efficacy of anticataract preparations. So far, such trials have been carried out with Phakan and two types of eye drops (preparations "A" and "B") in accordance with the conditions for controlled therapy studies. The procedure is explained taking the Phakan study as an example. Lens findings were evaluated by densitometric image analysis of Scheimpflug photographs of the anterior eye segment, made at different times during the trial. The validity of the data for statistical calculations was at first overrated. Mean values obtained with the method, however, correspond to the values expected: they show the required progression over longer periods. The reliability of the method was checked by taking into account the clinical observations and visual acuity tests on 35 patients (62 eyes) which had been under observation for a considerable period of time (up to 5.5 years). The results indicate clearly that Phakan can favorably influence opacities located in the lens cortex and that after a 9-month treatment even a prolonged effect (2-3 years) may be observed. With preparation "A" some indication - although not completely satisfactory - of efficacy in cases of cortical opacities was found. A one-year treatment with preparation "B" produced no differences as compared to untreated controls. However, it appears advisable to extend observation periods in future trials.

Topics: Amino Acids; Ascorbic Acid; Cataract; Clinical Trials as Topic; Densitometry; Double-Blind Method; Drug Combinations; Humans; Inositol; Ophthalmic Solutions; Pyridoxine; Time Factors; Visual Acuity

Topics: Amino Acids; Ascorbic Acid; Cataract; Clinical Trials as Topic; Drug Combinations; Humans; Inositol; Pyridoxine; Statistics as Topic

Topics: Adult; Aged; Amino Acids; Ascorbic Acid; Cataract; Clinical Trials as Topic; Double-Blind Method; Drug Combinations; Humans; Inositol; Middle Aged; Pyridoxine; Random Allocation

In this study, we studied effect of smoking on ascorbic acid level in aqueous humor. A cohort of 112 individuals undergoing cataract surgery for senile cataract (mean ± SD age-65 ± 8 years) was sub-grouped as smoker (n = 56) and non-smoker (n = 56) based on smoking habit. The aqueous humor sample was collected in beginning of the surgery and quantitative ascorbic acid estimation was done by colorimetric method (spectrophotometry at λ = 578 nm) using commercially available assay kits using the auto-analyzer assay procedure. The mean (±SD) aqueous humor ascorbic acid level was 1396 ± 629 μmol/L among non-smokers and 774 ± 436 μmol/L among smokers (p < 0.0001). The aqueous humor ascorbic acid concentration is significantly lower in smokers compared to non-smokers. The aqueous humor ascorbic acid concentration is affected by gender but not by age or morphology of cataract.

Topics: Aqueous Humor; Ascorbic Acid; Cataract; Humans; Non-Smokers; Smoking

Topics: Apoptosis; Ascorbic Acid; Cataract; Epithelial Cells; Epithelium; Humans; Lens, Crystalline; NF-kappa B; Oxidative Stress; Reactive Oxygen Species; Ultraviolet Rays

Compromised pumping function of the corneal endothelium, due to loss of endothelial cells, results in corneal edema and subsequent visual problems. Clinically and experimentally, oxidative stress may cause corneal endothelial decompensation after phacoemulsification. Additionally, in vitro and animal studies have demonstrated the protective effects of intraoperative infusion of ascorbic acid (AA). Here, we established a paraquat-induced cell damage model, in which paraquat induced reactive oxygen species (ROS) production and apoptosis in the B4G12 and ARPE-19 cell lines. We demonstrate that oxidative stress triggered autophagic flux blockage in corneal endothelial cells and that addition of AA ameliorated such oxidative damage. We also demonstrate the downregulation of Akt phosphorylation in response to oxidative stress. Pretreatment with ascorbic acid reduced the downregulation of Akt phosphorylation, while inhibition of the PI3K/Akt pathway attenuated the protective effects of AA. Further, we establish an in vivo rabbit model of corneal endothelial damage, in which an intracameral infusion of paraquat caused corneal opacity. Administration of AA via topical application increased its concentration in the corneal stroma and reduced oxidative stress in the corneal endothelium, thereby promoting corneal clarity. Our findings indicate a perioperative strategy of topical AA administration to prevent oxidative stress-induced damage, particularly for those with vulnerable corneal endothelia.

Topics: Animals; Apoptosis; Ascorbic Acid; Autophagy; Cataract; Cell Line; Cornea; Endothelial Cells; Humans; Oxidative Stress; Rabbits

Oxoaldehyde stress has recently emerged as a major source of tissue damage in aging and age-related diseases. The prevailing mechanism involves methylglyoxal production during glycolysis and modification of arginine residues through the formation of methylglyoxal hydroimidazolones (MG-H1). We now tested the hypothesis that oxidation of vitamin C (ascorbic acid or ASA) contributes to this damage when the homeostatic redox balance is disrupted especially in ASA-rich tissues such as the eye lens and brain. MG-H1 measured by liquid chromatography mass spectrometry is several fold increased in the lens and brain from transgenic mice expressing human vitamin C transporter 2 (hSVCT2). Similarly, MG-H1 levels are increased two- to fourfold in hippocampus extracts from individuals with Alzheimer's disease (AD), and significantly higher levels are present in sarkosyl-insoluble tissue fractions from AD brain proteins than in the soluble fractions. Moreover, immunostaining with antibodies against methylglyoxal hydroimidazolones reveals similar increase in substantia nigra neurons from individuals with Parkinson's disease. Results from an in vitro incubation experiment suggest that accumulated catalytic metal ions in the hippocampus during aging could readily accelerate ASA oxidation and such acceleration was significantly enhanced in AD. Modeling studies and intraventricular injection of

Topics: Adult; Aged; Aged, 80 and over; Aging; Aldehydes; Animals; Ascorbic Acid; Cataract; Humans; Mice; Mice, Transgenic; Middle Aged; Neurodegenerative Diseases

Cataracts are the most common ocular disorder in dogs. Phacoemulsification is the preferred treatment method among ophthalmologists, but the cellularity of the endothelium must be considered for its success, as endothelial lesions may produce permanent corneal decompensation. The objective of this study was to evaluate the effects of intracameral ascorbic acid, a known antioxidant, on the corneal endothelium of dogs undergoing phacoemulsification.. In all, 40 eyes from 20 dogs, males and females from 7 to 12 years of age, were assessed for mature cataracts.. Two groups were formed (n = 20): Group 1 (G1) received a balanced salt solution (BSS), whereas Group 2 (G2) received sterile ascorbic acid diluted in a BSS, at a final concentration of 0.001 m ascorbic acid. The corneal endothelium was assessed via non-contact specular microscopy at multiple time points before and after phacoemulsification. Cell density (cells/mm. With respect to the density of endothelial cells, both groups showed losses, but they were less severe in G2. There were no differences in corneal thickness. Hexagonality decreased significantly in the postoperative period in G1. Also in G1, the coefficient of variation of cell size increased significantly.. According to the results obtained, ascorbic acid minimizes cellular losses in the corneal endothelium.

Topics: Animals; Ascorbic Acid; Cataract; Dogs; Endothelium, Corneal; Female; Intraoperative Period; Male; Phacoemulsification; Postoperative Care

Cataracts are a major cause of blindness worldwide. As anti‑cataract pharmaceutical therapies require long‑term treatment, identifying anti‑cataract compounds that are ubiquitous in the human diet, have no adverse effects and are affordable, is of paramount importance. The present study focused on hesperetin and its derived compounds, hesperetin stearic acid ester (Hes‑S) and hesperetin oleic acid ester (Hes‑O), in order to investigate their therapeutic potential to treat cataracts in a selenite animal model. Thirteen‑day‑old Sprague Dawley rats were divided into 12 groups. Animals in groups 1 and 7 were subcutaneously injected with vehicle, those in groups 2 and 8 were administered hesperetin, those in groups 3 and 9 received stearic acid, those in groups 4 and 10 were injected with oleic acid, those in groups 5 and 11 were administered Hes‑S, and those in groups 6 and 12 received Hes‑O (10 nmol/kg body weight on days 0, 1 and 2). Animals in groups 7 to 12 were treated with sodium selenite (20 µmol/kg body weight given 4 h following the test compound treatment on day 0) to induce cataract. On day 6, rats had less severe central opacities and lower stage cataracts than rats in the selenite treatment‑only control groups. The levels of glutathione (GSH) and ascorbic acid (AsA) in lenses with selenite‑induced cataracts declined to one‑third of that of controls, and the reduction in GSH and AsA levels was rescued following hesperetin, Hes‑S or Hes‑O treatment, with concentrations remaining to 70‑80% of that of controls. However, there were no changes in the plasma levels of GSH and AsA following treatments. Administration of either hesperetin or hesperetin‑derived compounds prevented the reduction of chaperone activity in the lens, and rats treated with Hes‑S or Hes‑O treatment had significantly greater chaperone activity than hesperetin‑treated rats. Collectively, these results suggested that hesperetin and hesperetin‑derived compounds may be novel drug compounds that have the potential to prevent or delay the onset of cataracts.

Topics: Animals; Ascorbic Acid; Cataract; Female; Glutathione; Hesperidin; Rats; Rats, Sprague-Dawley; Selenious Acid

To measure ascorbic acid concentration in aqueous humor of patients with cataract after oral or intravenous vitamin C supplementation.. Forty-two eyes of 42 patients with senile cataract who underwent uncomplicated cataract surgery were enrolled. Patients (n = 14 each) were administered oral vitamin C (2 g), intravenous vitamin C (20 g) or no treatment (control group) on the day before surgery. Samples of aqueous humor (0.1 cm. The mean age at surgery was 62.5 years, with no difference among the three groups. The mean ± standard deviation concentrations of ascorbic acid in aqueous humor in the control and oral and intravenous vitamin C groups were 1347 ± 331 μmol/L, 1859 ± 408 μmol/L and 2387 ± 445 μmol/L, respectively. Ascorbic acid concentration was significantly lower in the control than in the oral (P < 0.01) and intravenous (P < 0.001) vitamin C groups and was significantly higher in the intravenous than in the oral vitamin C group (P < 0.05).. Ascorbic acid concentration in aqueous humor is increased by systemic vitamin C supplementation, with intravenous administration being more effective than oral administration.

Topics: Administration, Oral; Antioxidants; Aqueous Humor; Ascorbic Acid; Biomarkers; Cataract; Cataract Extraction; Chromatography, High Pressure Liquid; Female; Follow-Up Studies; Humans; Injections, Intravenous; Male; Middle Aged; Pilot Projects; Prospective Studies

This study investigated the ability of hesperetin, a natural flavonoid, to prevent selenite-induced cataracts in a rat model.. Animals were divided into four treatment groups: G1 (control group), G2 (hesperetin-treated group), G3 (selenite-induced cataract group), and G4 (hesperetin-treated selenite cataract group). Animals in the G1 and G3 groups were injected with vehicle alone, while those in the G2 and G4 groups received a subcutaneous injection of hesperetin (0.4 μg/g bodyweight on days 0, 1, and 2, corresponding to P13, P14, and P15). Sodium selenite (20 μmol/g bodyweight given 4 h after the hesperetin injection on day 0) was administered to rats in the G3 and G4 groups to induce cataract formation. Lenses were observed with slit-lamp microscopy, and filensin degradation and the decreased glutathione (GSH) and ascorbic acid levels in the lens were measured on day 6.. Lenses in the G3 group showed mature central opacity, while some lenses in the G4 group lacked central opacity and had lower-grade cataracts. All lenses in the G1 and G2 groups were transparent. Expression of the 94 kDa and 50 kDa forms of filensin was significantly decreased in the lenses in the G3 group compared with those in the G1 and G2 groups. Interestingly, these forms of filensin rescued the rat lenses in the G4 group. In the G3 group lenses, the GSH and ascorbic acid levels were lower than in the control group but were normalized in the G4 group lenses.. The results suggest that hesperetin can prevent selenite-induced cataract formation.

Topics: Animals; Antioxidants; Ascorbic Acid; Cataract; Disease Models, Animal; Eye Proteins; Female; Free Radical Scavengers; Glutathione; Hesperidin; Intermediate Filament Proteins; Lens, Crystalline; Oxidative Stress; Proteolysis; Rats; Rats, Sprague-Dawley; Sodium Selenite

Age-related cataract is a common disease among senior population. Vitamin C is the most effective reducing hydrosoluble antioxidant causing reduction in the levels of free radicals in crystaline lens. The aim of this study was to evaluate the age-related change of vitamin C (L-ascorbic acid) level in the aqueous humor of patients with senile cataract.. This prospective study included 74 patients, divided into 3 age groups, with age-related cataract, underwent routine phaco cataract surgery with intraocular lens implantation. Aqueous humor was aspirated from 74 eyes at the beginning of phacoemulsification. The levels of vitamin C (L-ascorbic acid) in aqueous humor were determined with high-performance liquid chromatography (HPLC).. The average age of pa- tients included in the study was 65 ± 9.85 years (54-87 years). The level of vitamin C in aqueous humor was 152.78 ± 7.0125 µg/mL in the group A (50-59 years), 134.15 ± 5.1569 µg/mL in the group B (60-69 years) and 106.51 ± 5.44 µg/mL in the group C (over 70 years).. The amount of vitamin C in aqueous humor of patients with age-related cataract is decreasing with age. There was a statistically significant change (p < 0.001) of vitamin C aqueous concentration in the patients of different age. This decrease could play a role in susceptibility to cataract formation in older population.

Topics: Age Factors; Aged; Antioxidants; Aqueous Humor; Ascorbic Acid; Cataract; Chromatography, Liquid; Female; Humans; Intraoperative Care; Lens, Crystalline; Male; Middle Aged; Phacoemulsification; Reproducibility of Results

Advanced glycation end products (AGEs) contribute to lens protein pigmentation and cross-linking during aging and cataract formation. In vitro experiments have shown that ascorbate (ASC) oxidation products can form AGEs in proteins. However, the mechanisms of ASC oxidation and AGE formation in the human lens are poorly understood. Kynurenines are tryptophan oxidation products produced from the indoleamine 2,3-dioxygenase (IDO)-mediated kynurenine pathway and are present in the human lens. This study investigated the ability of UVA light-excited kynurenines to photooxidize ASC and to form AGEs in lens proteins. UVA light-excited kynurenines in both free and protein-bound forms rapidly oxidized ASC, and such oxidation occurred even in the absence of oxygen. High levels of GSH inhibited but did not completely block ASC oxidation. Upon UVA irradiation, pigmented proteins from human cataractous lenses also oxidized ASC. When exposed to UVA light (320-400 nm, 100 milliwatts/cm(2), 45 min to 2 h), young human lenses (20-36 years), which contain high levels of free kynurenines, lost a significant portion of their ASC content and accumulated AGEs. A similar formation of AGEs was observed in UVA-irradiated lenses from human IDO/human sodium-dependent vitamin C transporter-2 mice, which contain high levels of kynurenines and ASC. Our data suggest that kynurenine-mediated ASC oxidation followed by AGE formation may be an important mechanism for lens aging and the development of senile cataracts in humans.

Topics: Animals; Ascorbic Acid; Cataract; Crystallins; Glycation End Products, Advanced; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Kynurenine; Lens, Crystalline; Mice; Oxidation-Reduction; Ultraviolet Rays

We have previously reported low concentrations of plasma ascorbate and low dietary vitamin C intake in the older Indian population and a strong inverse association of these with cataract. Little is known about ascorbate levels in aqueous humor and lens in populations habitually depleted of ascorbate and no studies in any setting have investigated whether genetic polymorphisms influence ascorbate levels in ocular tissues. Our objectives were to investigate relationships between ascorbate concentrations in plasma, aqueous humor and lens and whether these relationships are influenced by Single Nucleotide Polymorphisms (SNPs) in sodium-dependent vitamin C transporter genes (SLC23A1 and SLC23A2). We enrolled sixty patients (equal numbers of men and women, mean age 63 years) undergoing small incision cataract surgery in southern India. We measured ascorbate concentrations in plasma, aqueous humor and lens nucleus using high performance liquid chromatography. SLC23A1 SNPs (rs4257763, rs6596473) and SLC23A2 SNPs (rs1279683 and rs12479919) were genotyped using a TaqMan assay. Patients were interviewed for lifestyle factors which might influence ascorbate. Plasma vitamin C was normalized by a log10 transformation. Statistical analysis used linear regression with the slope of the within-subject associations estimated using beta (β) coefficients. The ascorbate concentrations (μmol/L) were: plasma ascorbate, median and inter-quartile range (IQR), 15.2 (7.8, 34.5), mean (SD) of aqueous humor ascorbate, 1074 (545) and lens nucleus ascorbate, 0.42 (0.16) (μmol/g lens nucleus wet weight). Minimum allele frequencies were: rs1279683 (0.28), rs12479919 (0.30), rs659647 (0.48). Decreasing concentrations of ocular ascorbate from the common to the rare genotype were observed for rs6596473 and rs12479919. The per allele difference in aqueous humor ascorbate for rs6596473 was -217 μmol/L, p < 0.04 and a per allele difference in lens nucleus ascorbate of -0.085 μmol/g, p < 0.02 for rs12479919. The β coefficients for the regression of log10 plasma ascorbate on aqueous humor ascorbate were higher for the GG genotype of rs6596473: GG, β = 1460 compared to carriage of the C allele, CG, β = 1059, CC, β = 1132, p interaction = 0.1. In conclusion we found that compared to studies in well-nourished populations, ascorbate concentrations in the plasma, aqueous humor and lens nucleus were low. We present novel findings that polymorphisms in SLC23A1/2 genes influenced ascorbate concentration

Topics: Adult; Aged; Alleles; Aqueous Humor; Ascorbic Acid; Cataract; Chromatography, High Pressure Liquid; DNA; Female; Gene Frequency; Genotype; Humans; Lens Nucleus, Crystalline; Male; Middle Aged; Plasma; Polymorphism, Genetic; Sodium-Coupled Vitamin C Transporters

We examined the associations of high-dose supplements of vitamins C and E and low-dose multivitamins with the risk of age-related cataract among 31,120 Swedish men, aged 45-79 years, in a population-based prospective cohort. Dietary supplement use was assessed from a questionnaire at baseline in 1998. During follow-up (January 1998-December 2006), 2,963 incident age-related cataract cases were identified. The multivariable-adjusted hazard ratio for men using vitamin C supplements only was 1.21 (95% confidence interval (CI): 1.04, 1.41) in a comparison with that of non-supplement users. The hazard ratio for long-term vitamin C users (≥10 years before baseline) was 1.36 (95% CI: 1.02, 1.81). The risk of cataract with vitamin C use was stronger among older men (>65 years) (hazard ratio = 1.92, 95% CI: 1.41, 2.60) and corticosteroid users (hazard ratio = 2.11, 95% CI: 1.48, 3.02). The hazard ratio for vitamin E use only was 1.59 (95% CI: 1.12, 2.26). Use of multivitamins only or multiple supplements in addition to vitamin C or E was not associated with cataract risk. These results suggest that the use of high-dose (but not low-dose) single vitamin C or E supplements may increase the risk of age-related cataract. The risk may be even higher among older men, corticosteroid users, and long-term users.

Topics: Adrenal Cortex Hormones; Age Factors; Aged; Alcohol Drinking; Ascorbic Acid; Cataract; Diet; Dietary Supplements; Educational Status; Humans; Incidence; Life Style; Male; Middle Aged; Prospective Studies; Risk Factors; Smoking; Surveys and Questionnaires; Sweden; Vitamin E; Vitamins; Waist Circumference

Cataract is among the major causes of vision impairment and blindness worldwide. Epidemiological studies support the role of antioxidants in the etiology of cataract, but the evidence for one specific antioxidant over another is inconsistent. Few studies have examined the association of cataract with fruit and vegetable intake with inconclusive results. In the present study, the relationship between cataract and fruit and vegetable intake and dietary and blood levels of carotenoids, vitamins C and E were examined in a Spanish Mediterranean population.. The present work is an analysis of data from 599 elderly ( ≥ 65 years) participants from the Spanish segment of the EUREYE study. This is a European multi-center cross-sectional population-based study. Cataract was diagnosed using a slit-lamp examination and defined as any lens opacity in either eye or evidence of its removal (cataract extraction). Energy-adjusted intake of fruit and vegetables and antioxidant vitamins was estimated using a semi-quantitative food frequency questionnaire. Plasma concentrations of vitamin C were analyzed by a colorimetric method and carotenoids and α-tocopherol by a HPLC method. The associations between cataract and quartiles of fruit and vegetable intake and plasma antioxidants were investigated using logistic regression models.. Of the 599 elderly recruited, 433 (73%) had cataract or cataract extraction, 54% were women and 46% were men. After adjustments, increasing quartiles of combined fruit and vegetable intake were associated with decreasing reduction of odds of cataract or cataract extraction, (P for trend = 0.008). Increasing quartiles of dietary intakes from 107 mg/d of vitamin C showed a significant decreasing association with prevalence of cataract or cataract extraction (P for trend = 0.047). For vitamin E, a protective association was found from intakes from 8 mg/d, but no linear trend was observed across quartiles of intake (P for trend = 0.944).. High daily intakes of fruit and vegetables and vitamins C and E were associated with a significantly decreased of the prevalence of cataract or cataract surgery. This study reinforces the WHO recommendations on the benefits of diets rich in fruit and vegetables.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Carotenoids; Cataract; Cross-Sectional Studies; Diet; Diet Records; Female; Fruit; Humans; Logistic Models; Male; Mediterranean Region; Prevalence; Spain; Vegetables; Vitamin E

We investigated whether decreased vitamin C (VC) in a mouse model increases lens opacity (cataract) induced by in vivo exposure to ultraviolet radiation type B (UVR-B). Senescence marker protein-30 (SMP30) knockout (KO) mice, which cannot synthesize VC due to genetic disruption of the gluconolactonase (GNL) gene, were divided into 2 groups: VC sufficient (VC (+)) and VC deficient (VC (-)). Starting at 1 month of age, these groups had free access to water containing 0.0375 and 1.5 g/L of VC, respectively. SMP30 KO VC (-), SMP30 KO VC (+), and wild-type (WT) mice, all 14 weeks of age, were unilaterally exposed in vivo to UVR-B (200 mW/cm(2)) for 100 s twice a week for 3 weeks (total: 1200 mJ/cm(2)). At 48 h after the last UVR-B exposure, cataract morphology was documented, and the ratio of cataract induction was quantified as the cataract area ratio (opacity area/anterior capsule). UVR-B exposure induced cataract mainly at anterior sub-capsular in SMP30 KO VC (-), SMP30 KO VC (+), and WT mice. In SMP30 KO VC (-) lenses the opacities were more extensive than in SMP30 KO VC (+) or WT lenses (cataract area ratios: 59.3% ± 10% vs. 32.2% ± 11.7% or 29.0% ± 9.0%; P < 0.01). In conclusion, VC depletion may increase the susceptibility to develop UVR-B induced cataracts in mice unable to endogenously produce VC.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Calcium-Binding Proteins; Carboxylic Ester Hydrolases; Cataract; Disease Models, Animal; Intracellular Signaling Peptides and Proteins; Lens, Crystalline; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Radiation Injuries, Experimental; Ultraviolet Rays

This was a preliminary study of the effects of antioxidant supplementation on the peroxidation status of the lens by investigating mRNA expression of anti-oxidative enzymes in the lens. The mRNA expression levels of glucose-6-phosphate dehydrogenase (G6PDH), β-actin (β-ACT) and 18S rRNA (18S) were measured in this study because they are common reference genes for measuring mRNA levels by means of a real-time reverse transcription polymerase chain reaction (RT-PCR) in various tissues. Thirteen patients with binocular cataracts of the same grade were included in the study after giving informed consent. A piece of the anterior capsule, along with a sample of lenticular epithelial cells (LECs), was collected as a pre-intake sample during cataract surgery. Ocuvite + Lutein(®), an antioxidant supplement, was administered orally beginning the day after surgery. Six weeks later, a piece of the anterior capsule along with a sample of LECs, was collected as a post-intake sample during cataract surgery of the opposite eye. RNA was purified from the homogenized samples, and cDNA was reverse transcribed to measure mRNA levels. The expression levels of G6PDH, 18S and β-ACT were measured using RT-PCR. The expression levels of G6PDH and 18S were significantly higher in the post-intake samples than they were in the pre-intake samples. Significant positive correlations between the expression levels of G6PDH and 18S were observed in both the pre- and post-intake samples. Following gender-specific analyses, the expression levels of G6PDH and 18S in the post-intake samples were found to be significantly higher among the female patients. A significant positive correlation between the expression levels of G6PDH and 18S was observed in the post-intake samples from the male patients. There were no significant changes in the gene expression levels of β-ACT after supplementation among male or female patients. β-ACT has been verified for use as a reference gene for measuring the effects of antioxidant supplementation in the lens by RT-PCR. Antioxidant supplementation was noted to increase G6PDH in the pentose phosphate cycle and 18S rRNA in the ribosome.

Topics: Actins; Administration, Oral; Aged; Anterior Capsule of the Lens; Antioxidants; Ascorbic Acid; Base Sequence; beta Carotene; Cataract; Cataract Extraction; Dietary Supplements; DNA Primers; DNA Probes; Drug Combinations; Female; Gene Expression Regulation; Glucosephosphate Dehydrogenase; Humans; Lutein; Male; Molecular Sequence Data; Niacin; Reverse Transcriptase Polymerase Chain Reaction; Riboflavin; RNA, Messenger; RNA, Ribosomal, 18S; Vitamin E

The immediate cause of the occurrence of cataract is unknown, but oxidative damage and effects of reactive oxygen species are considered important in its etiopathogenesis. Our research was aimed at testing the nonenzyme antioxidant power of corticonuclear lens blocks, with different types and different maturity of age-related cataract. Clinical and biochemical researches were carried out in 101 patients with age-related cataract. In corticonuclear lens blocks of the patient, the concentration of nonprotein and total-SH groups and the concentration of total vitamin C and dehydroascorbic acid (DHA) were determined; the current redox balance of dehydroascorbate/ascorbate and total antioxidant power measured by ferric-reducing ability were examined. In corticonuclear lens blocks with incipient cataract a significantly higher concentration of GSH, total SH groups, concentration of total vitamin C and ascorbic acid (AA), and ferric-reducing ability were measured. The measured concentration of DHA is higher than the concentration of AA in the lenses with the incipient and mature cataract. The concentration ratio of redox couple DHA/AA is higher in lenses with mature cataract, where the measured concentration of AA was lower than in the incipient cataract. Timely removal of DHA from the lens is important because of its potential toxicity as an oxidant. An increase of the current concentration of DHA/AA redox balance can be an indicator of oxidative stress.

Topics: Aged; Aged, 80 and over; Aging; Antioxidants; Ascorbic Acid; Cataract; Dehydroascorbic Acid; Female; Glutathione; Humans; Lens, Crystalline; Male; Middle Aged; Oxidants; Oxidation-Reduction; Oxidative Stress

Phytotherapy has played an important role in the management of diabetes and related complications. In the present study different fractions of Catharanthus roseus L. (Apocynaceae), Ocimum sanctum L. (Labiatae), Tinospora cordifolia Willd. (Menispermaceae), Aegle marmelos L. (Rutaceae), Ficus golmerata L. (Moraceae), Psoralea corlifolia L. (Fabaceae), Tribulus terrestris L. (Zygophyllaceae), and Morinda cetrifolia L. (Rubiaceae) were evaluated as possible inhibitors of aldose reductase (AR: a key enzyme implicated in cataractogenesis) and antioxidant agents. Anti-cataract activity of the selected plants was demonstrated using 'sugar induced lens opacity model' and the cytotoxicity studies were carried out using MTT assay. Among the tested plants, water extract of M. cetrifolia (IC50 0.132 mg/ml) exhibited maximum AR inhibitory activity as compared to other phytofractions which showed the activity in an IC50 range of 0.176-0.0.82 mg/ml. All the plant fractions showed considerable antioxidant potential. Sugar induced lens opacity studies revealed that, M. cetrifolia possess significant anti-cataract potential to maintain lens opacity as compared to glucose induced lens opacity in bovine lens model. The extract of the selected plants showed moderate cytotoxicity against HeLa cell line. Results of the present studies may find useful in converting botanicals into therapeutic modalities.

Topics: Aegle; Aldehyde Reductase; Animals; Ascorbic Acid; Cataract; Catharanthus; Cattle; Diabetes Complications; Disease Models, Animal; Enzyme Inhibitors; Ficus; Flavonoids; Free Radical Scavengers; HeLa Cells; Humans; Hypoglycemic Agents; Male; Menispermaceae; Morinda; Ocimum; Phenols; Phytotherapy; Plant Extracts; Plants, Medicinal; Psoralea; Rats; Tinospora; Tribulus

To examine the association between vitamin C and cataract in the Indian setting.. Population-based cross-sectional analytic study.. A total of 5638 people aged ≥60 years.. Enumeration of randomly sampled villages in 2 areas of north and south India to identify people aged ≥60 years. Participants were interviewed for socioeconomic and lifestyle factors (tobacco, alcohol, household cooking fuel, work, and diet); attended a clinical examination, including lens photography; and provided a blood sample for antioxidant analysis. Plasma vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid, and other antioxidants were measured by reverse-phase high-pressure liquid chromatography.. Cataract and type of cataract were graded from digital lens images using the Lens Opacity Classification System III (LOCS III), and cataract was classified from the grade in the worse eye of ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any cataract was defined as any unoperated or operated cataract.. Of 7518 enumerated people, 5638 (75%) provided data on vitamin C, antioxidants, and potential confounders. Vitamin C was inversely associated with cataract (adjusted odds ratio [OR] for highest to lowest quartile = 0.61; 95% confidence interval (CI), 0.51-0.74; P=1.1×10(-6)). Inclusion of other antioxidants in the model (lutein, zeaxanthin, retinol, β-carotene, and α-tocopherol) made only a small attenuation to the result (OR 0.68; 95% CI, 0.57-0.82; P < 0.0001). Similar results were seen with vitamin C by type of cataract: nuclear cataract (adjusted OR 0.66; CI, 0.54-0.80; P < 0.0001), cortical cataract (adjusted OR 0.70; CI, 0.54-0.90; P < 0.002), and PSC (adjusted OR 0.58; CI, 0.45-0.74; P < 0.00003). Lutein, zeaxanthin, and retinol were significantly inversely associated with cataract, but the associations were weaker and not consistently observed by type of cataract. Inverse associations were also observed for dietary vitamin C and cataract.. We found a strong association with vitamin C and cataract in a vitamin C-depleted population.. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Topics: Aged; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; beta Carotene; Cataract; Chromatography, High Pressure Liquid; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; India; Lutein; Male; Middle Aged; Prevalence; Risk Factors; Xanthophylls; Zeaxanthins

The human system possesses antioxidants that act harmoniously to neutralize the harmful oxidants. This study was aimed to evaluate the serum total antioxidant capacity (TAC) as a single parameter in Eales' disease (ED) and in an acute inflammatory condition such as uveitis and in cataract which is chronic, compared to healthy controls.. The TAC assay was done spectrophotometrically in the serum of Eales' disease cases (n=20) as well as in other ocular pathologies involving oxidative stress namely, uveitis and cataract (n=20 each). The oxidative stress measured in terms of TBARS, was correlated with the TAC. Individual antioxidants namely vitamin C, E and glutathione were also estimated and correlated with TAC.. TAC was found to be significantly lower in Eales' disease with active vasculitis (0.28 ± 0.09 mM, P<0.001), Eales' disease with healed vasculitis (0.67 ± 0.09 mM), uveitis (0.46 ± 0.09 mM, P<0.001) and cataract (0.53 ± 0.1 mM, P=0.001) compared to the healthy controls, with a TAC level of 0.77 ± 0.09 mM. The TAC was found to correlate positively with vitamin E levels (P=0.05), GSH (P=0.02) but not with vitamin C, as seen in ED cases. In ED cases supplemented with vitamin E and C, there was a significant increase in the TAC level (P=0.02).. The TAC measurement provided a comprehensive assay for establishing a link between the antioxidant capacity and the risk of disease as well as monitoring antioxidant therapy. This method is a good substitute for assay of individual antioxidants as it clearly gives the status of the oxidative stress in the disease process.

Topics: Adult; Ascorbic Acid; Cataract; Female; Glutathione; Humans; Male; Middle Aged; Neovascularization, Pathologic; Oxidative Stress; Retinal Vasculitis; Spectrophotometry; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Uveitis; Vitamin E

Previous experiments from our laboratory showed that the oral intake of selected guanidino compounds could block the formation of crystallin-bound advanced ascorbylation products. Here we tested whether these were also active when applied as eye drops.. Two month old hSVCT2 transgenic mice (n=10) were treated twice daily with one drop of 0.1% L-arginine, γ-guanidinobutyric acid (GBA), penicillamine (PA) or N-acetylcysteine (NAC) in one eye and vehicle only in the other eye. After seven months, lens crystallins were isolated, dialyzed, and proteolytically digested to determine the protein-bound fluorescence at 335/385 and 370/440 nm excitation/emission and the advanced glycation/ascorbylation endproducts carboxymethyl-lysine (CML), carboxyethyl-lysine (CEL), glucosepane, glyoxal, and methylglyoxal hydroimidazolones G-H1 and MG-H1. The topical uptake of L-arginine and NAC was also evaluated in vitro and in vivo in rabbit lens.. In hSVCT2 mice, L-arginine decreased 335/385 and 370/440 nm fluorescence by 40% (p<0.001), CML, CEL, and glucosepane crystallin crosslinks by 35% (p<0.05), 30% (p<0.05), and 37% (p<0.05), respectively, without affecting MG-H1 and G-H1. NAC decreased 335/385 nm fluorescence by 50% (p<0.001) but, like PA and GBA, had no effect on other modifications. L-Arginine uptake into rabbit eyes treated topically reached identical lenticular plateau levels (~400 nmol/g wet weight) at 0.5% and 2.0% but levels remained three times higher at 5 h at 2% versus 0.5% concentration, respectively. In vitro studies showed a 100 fold higher L-arginine level than NAC levels, implicating high affinity uptake of the former.. L-Arginine when applied both orally and topically is a potent and broad suppressor of advanced ascorbylation in the lens. Its uptake in rabbit lens upon topical application suggests transcorneal uptake into the human lens should be feasible for testing its potential anticataract properties in clinical trials.

Topics: Acetylcysteine; Administration, Topical; Aging; Animals; Arginine; Ascorbic Acid; Biological Transport, Active; Cataract; Crystallins; Gene Knock-In Techniques; Glycation End Products, Advanced; Guanidines; Humans; Lens, Crystalline; Mass Spectrometry; Mice; Mice, Transgenic; Ophthalmic Solutions; Penicillamine; Rabbits; Sodium-Coupled Vitamin C Transporters; Spectrometry, Fluorescence

Experimental animal studies have shown adverse effects of high-dose vitamin C supplements on age-related cataract.. We examined whether vitamin C supplements (approximately 1000 mg) and multivitamins containing vitamin C (approximately 60 mg) are associated with the incidence of age-related cataract extraction in a population-based, prospective cohort of women.. Our study included 24,593 women aged 49-83 y from the Swedish Mammography Cohort (follow-up from September 1997 to October 2005). We collected information on dietary supplement use and lifestyle factors with the use of a self-administrated questionnaire. Cataract extraction cases were identified by linkage to the cataract extraction registers in the geographical study area.. During the 8.2 y of follow-up (184,698 person-years), we identified 2497 cataract extraction cases. The multivariable hazard ratio (HR) for vitamin C supplement users compared with that for nonusers was 1.25 (95% CI: 1.05, 1.50). The HR for the duration of >10 y of use before baseline was 1.46 (95% CI: 0.93, 2.31). The HR for the use of multivitamins containing vitamin C was 1.09 (95% CI: 0.94, 1.25). Among women aged > or = 65 y, vitamin C supplement use increased the risk of cataract by 38% (95% CI: 12%, 69%). Vitamin C use among hormone replacement therapy users compared with that among nonusers of supplements or of hormone replacement therapy was associated with a 56% increased risk of cataract (95% CI: 20%, 102%). Vitamin C use among corticosteroid users compared with that among nonusers of supplements and corticosteroids was associated with an HR of 1.97 (95% CI: 1.35, 2.88).. Our results indicate that the use of vitamin C supplements may be associated with higher risk of age-related cataract among women.

Topics: Age Factors; Aged; Aged, 80 and over; Ascorbic Acid; Cataract; Cohort Studies; Dietary Supplements; Female; Humans; Incidence; Middle Aged; Prospective Studies; Risk Factors; Surveys and Questionnaires; Sweden

To investigate the association between smoking and subcapsular cataract and blood levels of cadmium and lead, and serum levels of vitamins C, E, and beta carotene in the middle-age male population.. The present study comprised 60 cataractous male patients aged 44-55 years who attended Mansoura University Ophthalmic Center. They were divided into two groups: the first group was comprised of 15 patients who had never smoked before with minimal exposure to cigarette smoking (control group), while the second group was comprised of 45 age and body mass index-matched smokers. Blood cadmium and lead concentrations were measured and their levels in the cataractous lenses were also estimated. The levels of some antioxidants, such as serum vitamins C, E, and beta carotene, were determined.. Cadmium had a statistically significant higher concentration in blood and lenses of smokers compared with that of non smokers (p < 0.0001). There was a significantly high accumulation of cadmium in the lenses of cataractous smokers reaching about a four-fold increase in heavy smokers (15.4 +/- 0.4 micromol/g) and nearly a three-fold increase in light smokers (10.1 +/- 0.4 micromol/g) when compared to that of nonsmokers (3.7 +/- 0.9 micromol/g). Regarding vitamins E, C, and beta carotene, a highly significant reduction was observed in smokers when compared with nonsmokers. There was a highly positive correlation between blood cadmium concentrations and lens cadmium levels, and blood lead concentrations and lens lead levels in heavy smokers.. Cadmium present in high concentrations among smokers was associated with the presence of cataracts, through induction of oxidative stress as evidenced by reduction of levels of some antioxidant studied in this work, such as vitamins E, C, and beta carotene. Thus, education of health care professionals and the public about the cataractogenic effect of cadmium is mandatory. Intake of various antioxidants may be helpful in reducing the risk of cataract formation.

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Cadmium; Cataract; Colorimetry; Humans; Lead; Lens, Crystalline; Male; Middle Aged; Prospective Studies; Smoking; Spectrophotometry, Atomic; Vitamin E; Vitamins

The present study was aimed at investigating the possible antioxidant potential of curcumin at a dose of 75 mg/kg body weight on selenite-induced cataract in experimental rat pups.. Group I: Control rat pups receiving physiological saline; Group II: Selenite-induced group (15 microM/kg body wt); Group III: Selenite-induced group co-treated with curcumin (single dose of curcumin orally 75 mg/kg body wt); Group IV: Selenite-induced animals post-treated (after 24 hrs) with curcumin at a dose mentioned for group III; Group V: Rat pups were pretreated with curcumin (dose as mentioned in Group III), 24 hrs before the administration of selenite. Encapsulated lenses liver, kidney, and serum were analyzed for antioxidant enzymes and malondialdehyde, a marker of lipid peroxidation.. Intraperitoneal injection of sodium selenite (15 microM/kg body wt) to 8-10-day-old rat pups led to severe oxidative stress in eye lens as evidenced by enhanced LPO levels that led to cataract formation. Sodium selenite also led to decrease in activities of SOD, GST, GPx, CAT with simultaneous decrease in the levels of GSH, vitamin C, and vitamin E. Treatment with curcumin (75 mg/kg body wt) led to a significant decrease in the levels of LPO, enzymic antioxidants, and nonenzymic antioxidants, which were similar to that of control.. Curcumin suppressed selenite-induced oxidative stress and cataract formation in rat pups. The presence of oxidative stress in selenite cataract development and its prevention by curcumin support the possibility that the natural consumption of curcumin in food can help prevent the onset of senile cataract.

Topics: Animals; Animals, Newborn; Antioxidants; Ascorbic Acid; Cataract; Curcumin; Disease Models, Animal; Glutathione; Injections, Intraperitoneal; Lens, Crystalline; Lipid Peroxidation; Male; Oxidative Stress; Oxidoreductases; Rats; Rats, Wistar; Sodium Selenite; Vitamin E

To establish the antioxidant status of the aqueous humour in glaucoma associated with exfoliation syndrome (XFG) and to compare it to primary open-angle glaucoma (POAG) and cataract patients.. Patients were diagnosed with POAG, XFG, or cataract (n=25 for each group). Total reactive antioxidant potential (TRAP) was measured by chemiluminescence. Ascorbic acid levels and the activities of catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD) were measured spectrophotometrically.ResultsTRAP value was lower in XFG (28+/-2 microM Trolox) than in POAG (55+/-8 microM Trolox; P<0.001). TRAP values in both glaucomas were lower than the cataract value (124+/-5 microM Trolox; P<0.001). A decrease in ascorbic acid was measured in XFG (230+/-20 microM) compared with POAG (415+/-17 microM; P<0.001). Ascorbic acid in both glaucomas was lower than in cataract (720+/-30 microM; P<0.001). A significant increase in GPx was found in XFG (30+/-2 U/ml) compared with POAG (16+/-3 U/ml). GPx activity in both glaucomas was increased when compared with cataracts (6+/-2 U/ml; P<0.001). A significant increase of 67% in SOD activity was observed in the glaucoma group vscataract group (27+/-3 U/ml; P<0.001), but no changes were found between both glaucomas.. The antioxidant status of the aqueous humour may play a role in the pathophysiology of both glaucomas.

Topics: Aged; Aged, 80 and over; Antioxidants; Aqueous Humor; Ascorbic Acid; Catalase; Cataract; Exfoliation Syndrome; Female; Glaucoma; Glaucoma, Open-Angle; Glutathione Peroxidase; Humans; Luminescence; Male; Superoxide Dismutase

Dietary antioxidant vitamins, in particular vitamin C, could play a role in preventing the onset or progression of age-related visual impairment. The aim of this study was to determine the plasma ascorbic acid levels in normal individuals and in senile cataract patients.. The test group included 50 cataract patients, while the control group members were selected among medical staff and patients' companions after age matching with the test group. Questionnaire forms contained age, sex, and location of residency (urban or rural) inquiries. Five milliliters of drawn blood was centrifuged, and plasma ascorbic acid level was measured by spectrophotometer. Statistical analysis of plasma ascorbic acid concentrations were done by paired test.. The mean plasma ascorbic acid level in the test group was 0.96 +/- 0.08 mg/dl and 1.12 +/- 0.15 mg/dl in the control group. Ascorbic acid level in the test group was significantly lower than the control group and p value = 0.00001. Aging had a reverse relation with plasma ascorbic acid level in males, while it showed no significant alterations in females. Rural compared with urban and females compared to males showed higher levels of plasma ascorbic acid.. This study revealed that plasma ascorbic acid level in cataract patients was lower than normal individuals. Antioxidant vitamins, in particular vitamin C, found in Mediterranean fruits and vegetables, can help with the prevention of cataracts, which is a major health service burden in many countries.

Topics: Age Factors; Aged; Aging; Ascorbic Acid; Biomarkers; Cataract; Disease Progression; Female; Humans; Male; Middle Aged; Spectrophotometry

To investigate the rate and mechanism of oxygen consumption by the vitreous.. Oxygen consumption was measured with a microrespirometer. Vitreous ascorbate was measured spectrophotometrically and by gas chromatography-mass spectrometry. Vitreous degeneration was related to the rate of oxygen consumption and ascorbate concentration in samples obtained during vitrectomy.. Prolonged exposure to oxygen or treatment with ascorbate oxidase eliminated oxygen consumption by the vitreous. Adding ascorbate restored oxygen consumption. Oxygen consumption persisted after boiling or treating the vitreous with the chelating agents EDTA and deferoxamine. In patients undergoing retinal surgery, liquefaction of the vitreous and previous vitrectomy were associated with decreased ascorbate concentration and lower oxygen consumption.. Ascorbate in the vitreous decreases exposure of the lens to oxygen. The catalyst for this reaction is not known, although free iron may contribute. The gel state of the vitreous preserves ascorbate levels, thereby sustaining oxygen consumption. Vitrectomy or advanced vitreous degeneration may increase exposure of the lens to oxygen, promoting the progression of nuclear cataracts.. Determining how the eye is protected from nuclear cataracts should suggest treatments to reduce their incidence.

Topics: Ascorbate Oxidase; Ascorbic Acid; Cataract; Gas Chromatography-Mass Spectrometry; Gels; Humans; Oxygen; Oxygen Consumption; Retinal Diseases; Vitrectomy; Vitreous Body

Oxidative stress has been implicated in cataractogenesis. Long-term intake of antioxidants may offer protection against cataract.. We investigated relations between antioxidant nutrient intakes measured at baseline and the 10-y incidence of age-related cataract.. During 1992-1994, 3654 persons aged >or=49 y attended baseline examinations of the Blue Mountains Eye Study (82.4% response). Of these persons, 2464 (67.4%) participants were followed >or=1 time after the baseline examinations (at either 5 or 10 y). At each examination, lens photography was performed and questionnaires were administered, including a 145-item semiquantitative food-frequency questionnaire. Antioxidants, including beta-carotene, zinc, and vitamins A, C, and E, were assessed. Cataract was assessed at each examination from lens photographs with the use of the Wisconsin Cataract Grading System. Nuclear cataract was defined for opacity greater than standard 3. Cortical cataract was defined as cortical opacity >or= 5% of the total lens area, and posterior subcapsular (PSC) cataract was defined as the presence of any such opacity.. Participants with the highest quintile of total intake (diet + supplements) of vitamin C had a reduced risk of incident nuclear cataract [adjusted odds ratio (OR): 0.55; 95% CI: 0.36, 0.86]. An above-median intake of combined antioxidants (vitamins C and E, beta-carotene, and zinc) was associated with a reduced risk of incident nuclear cataract (OR: 0.51; 95% CI: 0.34, 0.76). Antioxidant intake was not associated with incident cortical or PSC cataract.. Higher intakes of vitamin C or the combined intake of antioxidants had long-term protective associations against development of nuclear cataract in this older population.

Topics: Aged; Antioxidants; Ascorbic Acid; Australia; Cataract; Diet; Educational Status; Energy Intake; Feeding Behavior; Female; Follow-Up Studies; Health Surveys; Humans; Incidence; Male; Middle Aged; Oxidative Stress; Smoking; Surveys and Questionnaires

Several studies on cataract have suggested that antioxidant micronutrients such as alpha-tocopherol, retinol and ascorbic acid may help to protect against cataractogenesis. Our objective was to determine the serum concentration of these antioxidant vitamins in subjects with cataract to see if there is any correlation between the levels of essential vitamins and the development of cataract.. The study was performed on a total of 88 patients and healthy controls who were given physical examinations that included a complete eye examination. Ascorbic acid was measured in serum with UV/Vis spectrophotometry, and fat-soluble vitamins were measured in serum by high-performance liquid chromatography according to previously published methods.. The mean serum concentration of alpha-tocopherol in patients (9.16 +/- 2.53 microg/ml) with cataract was lower than in the control group (p < 0.001). Patients had a moderately lower ascorbic acid concentration than the control group, which was not statistically significant. The subjects' serum retinol levels were similar to control group levels and not statistically significant.. While this is a small-scale case study it can nonetheless be viewed as presenting support to help narrow the possibility that antioxidative agents may play a role in delaying cataract formation.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; Case-Control Studies; Cataract; Chromatography, High Pressure Liquid; Female; Humans; Male; Middle Aged; Nutrition Assessment; Nutritional Status; Risk Factors; Vitamin A

Topics: Ascorbic Acid; Carotenoids; Cataract; Diet Surveys; Double-Blind Method; Feeding Behavior; Health Personnel; Humans; Incidence; Lutein; Nutrition Assessment; Risk Assessment; Surveys and Questionnaires; United States; Vitamin E; Women's Health; Xanthophylls; Zeaxanthins

To estimate the in vitro level of L-ascorbic acid radical in lenses of patients with senile or diabetic cataract using EPR (Electron Paramagnetic Resonance) spectroscopy.. 24 human cataractous nuclei obtained during extracapsular removal were used. 5 of them (21%) were from diabetic patients. The analysis was carried out at the Department of Medical Physics of the Pomeranian Medical University using EPR spectroscopy. The in vitro level of L-ascorbic acid radical was calculated as the number of unpaired spins in the lens calculated in units x 10(16)/gram (spin/g), which is proportional to the in vivo level of vitamin C in lenses.. The average L-ascorbic acid radical level in lenses of diabetic patients amounted 0.53 x 10(16) spin/g +/- 0.22 x 10(16) spin/g, and was lower than in group of non-diabetic patients in which it ranged 0.87 x 10(16) spin/g +/- 0.31 x 10(16) spin/g (p = 0.036). There was no significant correlation between L-ascorbic acid radical level and sex, age or visual acuity in these two groups of patients.. (1) EPR spectroscopy can be used to determine the in vitro level of L-ascorbic acid radical in human lenses. (2) The in vitro L-ascorbic acid radical level in cataract lenses of patients with diabetes was lower than in patients without diabetes. (3). Lower in vitro level of L-ascorbic acid radical in lenses of patients with diabetes means lower in vivo level of vitamin C, what suggests an increased intensity of free radical reactions in the group of patients with diabetes than in the group without diabetes.

Topics: Aged; Ascorbic Acid; Cataract; Diabetes Complications; Electron Spin Resonance Spectroscopy; Female; Free Radicals; Humans; In Vitro Techniques; Lens, Crystalline; Male

To study if ascorbate supplementation decreases ultraviolet radiation (UVR)-induced cataract development in the guinea pig.. Sixty 6-9-week-old pigmented guinea pigs received drinking water supplemented with or without 5.5 mm l-ascorbate for 4 weeks. After supplementation, 40 animals were exposed unilaterally in vivo under anaesthesia to 80 kJ/m(2) UVR-B. One day later, the animals were killed and lenses were extracted. Degree of cataract was quantified by measurement of intensity of forward lens light scattering. Lens ascorbate concentration was determined with high-performance liquid chromatography (HPLC) with UVR detection at 254 nm. Twenty animals were used as non-exposed control.. Supplementation increased lens ascorbate concentration significantly. In UVR-exposed animals, mean 95% confidence intervals (CIs) for animal-averaged lens ascorbate concentration (micromol/g wet weight lens) were 0.54 +/- 0.07 (no ascorbate) and 0.83 +/- 0.05 (5.5 mm ascorbate). In non-exposed control animals, mean 95% CIs for animal-averaged lens ascorbate concentration (micromol/g wet weight lens) were 0.72 +/- 0.12 (0 mm ascorbate) and 0.90 +/- 0.15 (5.5 mm ascorbate). All non-exposed lenses were devoid of cataract. Superficial anterior cataract developed in all UVR-exposed lenses. The lens light scattering was 39.2 +/- 14.1 milli transformed equivalent diazepam concentration (m(tEDC)) without and 35.9 +/- 14.0 m(tEDC) with ascorbate supplementation.. Superficial anterior cataract develops in lenses exposed to UVR-B. Ascorbate supplementation is non-toxic to both UVR-B-exposed lenses and non-exposed control lenses. Ascorbate supplementation does not reduce in vivo lens forward light scattering secondary to UVR-B exposure in the guinea pig.

Topics: Animals; Ascorbic Acid; Cataract; Drinking; Guinea Pigs; Lens, Crystalline; Light; Radiation Injuries, Experimental; Scattering, Radiation; Ultraviolet Rays; Water

To examine in prospective data the relation between dietary intake of carotenoids and vitamins C and E and the risk of cataract in women.. Dietary intake was assessed at baseline in 39,876 female health professionals by using a detailed food frequency questionnaire. A total of 35,551 women provided detailed information on antioxidant nutrient intake from food and supplements and were free of a diagnosis of cataract. The main outcome measure was cataract, defined as an incident, age-related lens opacity responsible for a reduction in best-corrected visual acuity in the worse eye to 20/30 or worse based on self-report confirmed by medical record review.. A total of 2031 cases of incident cataract were confirmed during a mean of 10 years of follow-up. Comparing women in the extreme quintiles, the multivariate relative risk of cataract was 0.82 (95% confidence interval, 0.71-0.95; test for trend, P = .04) for lutein/zeaxanthin and 0.86 (95% confidence interval, 0.74-1.00; test for trend, P = .03) for vitamin E from food and supplements.. In these prospective observational data from a large cohort of female health professionals, higher dietary intakes of lutein/zeaxanthin and vitamin E from food and supplements were associated with significantly decreased risks of cataract.

Topics: Ascorbic Acid; Carotenoids; Cataract; Diet Surveys; Double-Blind Method; Feeding Behavior; Female; Health Personnel; Humans; Incidence; Lutein; Middle Aged; Nutrition Assessment; Prospective Studies; Risk Assessment; Surveys and Questionnaires; United States; Vitamin E; Women's Health; Xanthophylls; Zeaxanthins

Senile cataracts are associated with oxidation, fragmentation, cross-linking, insolubilization, and yellow pigmentation of lens crystallins. This process is partially explained by advanced glycation end products (AGEs) from ascorbic acid (ASA), as the authors unequivocally demonstrated in an hSVCT2 transgenic mouse. The authors present the first pharmacologic intervention study against ascorbylation in these mice.. Five groups of mice from 2 to 9 months of age (10 mice/group) were fed a diet containing 0.1% (wt/wt) aminoguanidine, pyridoxamine, penicillamine, and nucleophilic compounds NC-I and NC-II. AGEs were determined in crystallin digests using high-performance liquid chromatography, liquid chromatography-mass spectrometry, or gas chromatography-mass spectrometry. Lens protein extract was incubated in vitro with ASA or dehydroascorbic acid.. The ASA level increased approximately 10-fold in all groups and was unaffected by treatment. AGEs were increased several-fold in transgenic compared with control lenses. Body weight, food intake, lenticular glutathione, and glycated lysine level were unaltered. In vitro, all compounds inhibited AGE formation. In vivo, NC-I and NC-II significantly decreased protein fluorescence at lambda(ex)335/(em)385 (P = 0.045, P = 0.017, respectively) and lambda(ex)370/(em)440 (P = 0.029, P = 0.007, respectively). Other inhibitors had no effect. After 7 months, only NC-I and NC-II induced a 50% reduction in pentosidine (P = NS for NC-I; P = 0.035 for NC-II). NC-I also decreased carboxymethyllysine (P = 0.032) and carboxyethyllysine (P = NS). Fluorescent cross-link K2P was decreased by NC-I, NC-II, aminoguanidine, and pyridoxamine (P = NS).. Pharmacologically blocking protein ascorbylation with absorbable guanidino compounds is feasible and may represent a new strategy for the delay of age-related nuclear sclerosis of the lens.

Topics: Aging; Animals; Antioxidants; Ascorbic Acid; Cataract; Chromatography, High Pressure Liquid; Crystallins; Gas Chromatography-Mass Spectrometry; Glycation End Products, Advanced; Lens, Crystalline; Mice; Mice, Inbred C57BL; Mice, Transgenic; Spectrometry, Fluorescence

To examine the association of blood antioxidants with cataract.. Cross-sectional study of people aged >or=50 years identified from a household enumeration of 11 randomly sampled villages in North India. Participants were interviewed for putative risk factors (tobacco, alcohol, biomass fuel use, sunlight exposure, and socioeconomic status) and underwent lens photography and blood sampling. Lens photographs (nuclear, cortical, and posterior subcapsular) were graded according to the Lens Opacities Classification System (LOCS II). Cataract was defined as LOCS II grade >or=2 for any opacity or ungradable, because of dense opacification or history of cataract surgery. People without cataract were defined as LOCS II <2 on all three types of opacity, with absence of previous surgery.. Of 1443 people aged >or=50 years, 94% were interviewed, 87% attended an eye examination, and 78% gave a blood sample; 1112 (77%) were included in the analyses. Compared with levels in Western populations, antioxidants were low, especially vitamin C. Vitamin C was inversely associated with cataract. Odds ratios (OR) for the highest (>or=15 micromol/L) compared with the lowest (

Topics: Aged; Ascorbic Acid; Body Constitution; Carotenoids; Cataract; Chromatography, High Pressure Liquid; Cross-Sectional Studies; Female; Humans; India; Male; Middle Aged; Odds Ratio; Photography; Risk Factors; Rural Population; Surveys and Questionnaires; Vitamin A

In Western countries, many epidemiological studies have demonstrated that specific dietary nutrients are associated with the risk of developing age-related cataracts. These reports have suggested that dietary antioxidant vitamins, in particular vitamin C, can play a role in preventing the onset or progression of age-related visual impairment. However, few prospective studies have examined this relationship in a general Asian population. Therefore, in this study, we investigated whether dietary vitamin C was associated with a lower incidence of age-related cataracts by performing a 5-year prospective population-based analysis using data from a cohort of over 30,000 Japanese residents recruited to the Japan Public Health Center-based Prospective Study (JPHC Study) cohort I.. We carried out a prospective analysis of the association between vitamin C intake and age-related cataracts among middle-aged Japanese, to study the effects of dietary antioxidants in an Asian population.. This 5-year population-based study included 16,415 men and 18,771 women (aged 45-64 years), who were recruited onto the JPHC Study and had not reported cataracts in baseline surveys. Vitamin C was calculated from the nutrient intake assessed by self-administered food-frequency questionnaires (FFQ). Self-reported questionnaires were used to assess two endpoints: diagnosis or extraction of cataracts.. At follow-up, 216 men and 551 women reported new diagnoses, and 110 men and 187 women reported extractions of cataracts. For both endpoints, a higher vitamin C intake was associated with a reduced incidence of cataracts in both sexes. After adjusting for potential confounding factors, the multivariate odds ratios (ORs) for men and women in the highest quintiles of energy-adjusted vitamin C intake, relative to the lowest quintiles, were 0.65 (95% CI, 0.42-0.97) and 0.59 (95% CI, 0.43-0.89) for cataract diagnoses, and 0.70 (95% CI, 0.44-1.20) and 0.64 (95% CI, 0.41-0.94) for cataract extractions, respectively.. Dietary vitamin C intake might lower the risk of age-related cataracts among middle-aged Japanese.

Topics: Aging; Antioxidants; Ascorbic Acid; Cataract; Cataract Extraction; Cohort Studies; Diet; Diet Surveys; Dose-Response Relationship, Drug; Female; Humans; Japan; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Prevalence; Prospective Studies; Risk Factors; Surveys and Questionnaires

Ascorbic acid in aqueous humor of the eye has a role as an antioxidant in delaying cataract formation. In a cross-sectional comparative study, ascorbic acid levels from aqueous humor and venous blood obtained from patients with cataracts in mountainous regions (1,300-2,000 meters) and subtropical lowlands (<100 meters) of Nepal were measured spectrophotometrically with the objective of comparing the levels of aqueous humor ascorbic acid in patients with cataracts from these two diverse geographical regions. Of 131 patients included in the study, 59 were from the mountainous region of Nepal (Group A) and 72 were from the subtropical lowlands (Group B). The mean (+/- SD) plasma ascorbic acid level (mg%) of the subjects in Group A was 0.65 (+/- 0.20) and Group B was 0.85 (+/- 0.31). The aqueous ascorbic acid levels ranged from 12-28 mg % (mean +/-SD = 17.5+/-4.52) and 14-50 mg % (mean +/-SD =23.47+/-8.66) in Groups A and B, respectively. The difference of the plasma and aqueous humor ascorbic acid levels between the two groups was statistically significant (p<0.01). The plasma and aqueous humor ascorbic acid levels in the people with cataracts from the mountainous region of Nepal were significantly lower than those from subtropical lowlands. This may be because of the effect of high altitude and ultraviolet rays on ascorbic acid metabolism.

Topics: Altitude; Aqueous Humor; Ascorbic Acid; Cataract; Cross-Sectional Studies; Humans; Nepal; Tropical Climate

Topics: Antioxidants; Ascorbic Acid; Cataract; Clinical Trials as Topic; Dietary Supplements; Eye Diseases; Glaucoma; Humans; Macular Degeneration; Risk Factors; Smoking; Vitamin E; Vitamins

We previously reported chromatographic evidence supporting the similarity of yellow chromophores isolated from aged human lens proteins, early brunescent cataract lens proteins and calf lens proteins ascorbylated in vitro [Cheng, R. et al. Biochimica et Biophysica Acta 1537, 14-26, 2001]. In this paper, new evidence supporting the chemical identity of the modified amino acids in these protein populations were collected by using a newly developed two-dimensional LC-MS mapping technique supported by tandem mass analysis of the major species. The pooled water-insoluble proteins from aged normal human lenses, early stage brunescent cataract lenses and calf lens proteins reacted with or without 20 mM ascorbic acid in air for 4 weeks were digested with a battery of proteolytic enzymes under argon to release the modified amino acids. Aliquots equivalent to 2.0 g of digested protein were subjected to size-exclusion chromatography on a Bio-Gel P-2 column and four major A330nm-absorbing peaks were collected. Peaks 1, 2 and 3, which contained most of the modified amino acids were concentrated and subjected to RP-HPLC/ESI-MS, and the mass elution maps were determined. The samples were again analyzed and those peaks with a 10(4) - 10(6) response factor were subjected to MS/MS analysis to identify the daughter ions of each modification. Mass spectrometric maps of peaks 1, 2 and 3 from cataract lenses showed 58, 40 and 55 mass values, respectively, ranging from 150 to 600 Da. Similar analyses of the peaks from digests of the ascorbylated calf lens proteins gave 81, 70 and 67 mass values, respectively, of which 100 were identical to the peaks in the cataract lens proteins. A total of 40 of the major species from each digest were analyzed by LC-MS/MS and 36 were shown to be identical. Calf lens proteins incubated without ascorbic acid showed several similar mass values, but the response factors were 100 to 1000-fold less for every modification. Based upon these data, we conclude that the majority of the major modified amino acids present in early stage brunescent Indian cataract lens proteins appear to arise as a result of ascorbic acid modification, and are presumably advanced glycation end-products.

Topics: Amino Acids; Ascorbic Acid; Cataract; Chromatography, Liquid; Crystallins; Echocardiography; Glycosylation; Health; Humans; Mass Spectrometry; Molecular Weight; Peptide Fragments

To investigate the maximum tolerable dose (MTD) for cataract induced by ultraviolet radiation-B (UVB) in 7-week-old albino rats and to study the effect of UVB eye exposure on lens ascorbate content.. Fifty 7-week-old albino Sprague Dawley rats were unilaterally exposed in vivo to 300-nm UVB under anaesthesia, receiving 0, 0.25, 3.5, 4.3 and 4.9 kJ/m(2). The MTD was estimated based on lens forward light scattering measurements. Lens ascorbate content was determined in the processed lens using high performance liquid chromatography with UVR detection.. Animals exposed to UVB doses >or=3.5 kJ/m(2) developed cortical cataracts. The MTD for avoidance of UVB-induced cataract was estimated to 3.01 kJ/m(2). UVB exposure decreased lens ascorbate concentration in the exposed lens in line with UVB dose, H(e), according to the models: C = C(NonCo) + C(Co)e(-kH(e) ) for exposed lenses; C = C(NonCo) + C(Co) for non-exposed lenses, and C(d) = C(Co)(e(-kH(e) ) - 1). Parameters for consumable and non-consumable ascorbate were estimated to C(NonCo) = 0.04 and C(Co) = 0.11 micromol/g wet weight of lens. For lens ascorbate difference, tau = 1/k = 0.86 kJ/m(2). A total of 63% of UVB consumable ascorbate has been consumed after only tau = 0.86 kJ/m(2), while MTD(2.3 : 16) = 3.01 kJ/m(2), indicating that ascorbate decrease is in the order of 3.5 times more sensitive to detecting UVR damage in the lens than forward light scattering.. The MTD for avoidance of UVB-induced cataract in the 7-week-old albino Sprague Dawley rat was estimated to be 3.01 kJ/m(2). In vivo UVB exposure of the rat eye decreases lens ascorbate content following an exponential decline, and suprathreshold doses cause greater effect than subthreshold doses.

Topics: Animals; Ascorbic Acid; Cataract; Chromatography, High Pressure Liquid; Dose-Response Relationship, Radiation; Female; Lens, Crystalline; Maximum Tolerated Dose; Radiation Injuries, Experimental; Rats; Rats, Sprague-Dawley; Ultraviolet Rays

Senile cataracts are associated with progressive oxidation, fragmentation, cross-linking, insolubilization, and yellow pigmentation of lens crystallins. We hypothesized that the Maillard reaction, which leads browning and aroma development during the baking of foods, would occur between the lens proteins and the highly reactive oxidation products of vitamin C. To test this hypothesis, we engineered a mouse that selectively overexpresses the human vitamin C transporter SVCT2 in the lens. Consequently, lenticular levels of vitamin C and its oxidation products were 5- to 15-fold elevated, resulting in a highly compressed aging process and accelerated formation of several protein-bound advanced Maillard reaction products identical with those of aging human lens proteins. These data strongly implicate vitamin C in lens crystallin aging and may serve as a model for protein aging in other tissues particularly rich in vitamin C, such as the hippocampal neurons and the adrenal gland. The hSVCT2 mouse is expected to facilitate the search for drugs that inhibit damage by vitamin C oxidation products.

Topics: Animals; Ascorbic Acid; Base Sequence; Cataract; Crystallins; Dehydroascorbic Acid; DNA Primers; Humans; Lens, Crystalline; Maillard Reaction; Mice; Mice, Transgenic; Organic Anion Transporters, Sodium-Dependent; Reactive Oxygen Species; Recombinant Proteins; Sodium-Coupled Vitamin C Transporters; Symporters

This study investigated the relationship between the intake of antioxidant nutrients and the suffering of cataracts in 177 institutionalized elderly people (61 men and 116 women) aged > or = 65 years. Dietary intake was monitored for 7 consecutive days using a "precise individual weighing" method. Subjects, who during their earlier years were exposed by their work to sunlight, had a greater risk of suffering cataracts (OR = 3.2; CI: 1.1-9.3, P < 0.05) than those who worked indoors. A relationship was found between increased vitamin C intake and a reduced prevalence of cataracts (i.e., when comparing those above P95 for vitamin C intake with those below P5; (OR = 0.08; CI: 0.01-0.75, P 0.05). Among subjects with cataracts, 12.1% had vitamin C intakes of < 61 mg/day (P10) and only 2.2% had intakes of > 183 mg/day (P95) (p < 0.01). Subjects who consumed > 3290 microg/day (P95) of lutein were less likely to have cataracts (OR = 0.086; CI: 0.007-1.084; p < 0.05) than those whose consumption was < 256 microg/day (P5). In men, high intakes of zeaxanthin seemed to provide a protective effect against the problem (OR = 0.96; CI: 0.91-0.99; p < 0.05). The results suggest an association exists between exposure to sunlight and the development of cataracts, and that vitamin C, lutein, and zeaxanthin offer some protection against this disorder.

Topics: Aged; Aged, 80 and over; Aging; Antioxidants; Ascorbic Acid; Cataract; Diet; Diet Surveys; Female; Geriatric Assessment; Humans; Lutein; Male; Odds Ratio; Sex Distribution; Spain; Sunlight; Xanthophylls; Zeaxanthins

Moderate exercise and vitamin C and E (VCE) supplementation can be beneficial to diabetes due to reducing free radical production in lens and kidney of diabetic pregnant rats. We investigated the effect of VCE supplementation and moderate exercise on lipid peroxidation (MDA) and scavenging enzyme activity in the kidneys and lens of STZ-induced diabetic pregnant rats. Fifty female Wistar rats were used and were randomly divided into five groups. First and second were used as the control and pregnant control group. Third group was the pregnant diabetic group. The fourth group was the diabetic-pregnant-exercise group. VCE-supplemented feed was given to pregnant-diabetic-exercise rats constituting the fifth group. Animals in the exercised groups were moderately exercised daily on a treadmill (16.1 m/min, 45 min/d) for three weeks (five days a week). Diabetes was induced on day zero of the study. Plasma, lens, and kidney samples were taken from all animals on day 20. Exercise and administration of VCE to pregnant diabetic rats resulted in significant decrease in the albumin and total protein values and the elevated MDA, plasma creatinine, and urea levels as an indicator of oxidative stress and renal functional parameters. Exercise and VCE supplementation also increased glutathione peroxidase (GSH-Px), reduced glutathione (GSH), vitamin E, and beta-carotene levels in the kidney, GSH-Px and GSH in the lens, the albumin and total protein values in plasma. In the diabetic pregnant animals, the decreased vitamins A and E concentration and GSH levels in kidney, creatinine, and urea values in plasma did not improve through exercise only although their concentrations were increased by VCE supplementation. Kidney weight did not also affect either by exercise or VCE supplementation. In conclusion, these results suggest that exercise plus VCE affects antioxidant metabolism and reduces lipid peroxidation, thereby improving the damage caused by oxidative stress involved in the pathogenesis of lens and kidney in diabetic pregnant rats. Moderate exercise with dietary VCE may play a role in preventing nephropathy and cataract formation in diabetic pregnant rat.

Topics: Animals; Antioxidants; Ascorbic Acid; Cataract; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Diet; Drug Combinations; Female; Motor Activity; Oxidative Stress; Pregnancy; Pregnancy, Animal; Rats; Rats, Wistar; Vitamin E

Post-translational modifications of proteins take place during the aging of human lens. The present study describes a newly isolated glycation product of lysine, which was found in the human lens. Cataractous and aged human lenses were hydrolyzed and fractionated using reverse-phase and ion-exchange high performance liquid chromatography (HPLC). One of the nonproteinogenic amino acid components of the hydrolysates was identified as a 3-hydroxypyridinium derivative of lysine, 2-ammonio-6-(3-oxidopyridinium-1-yl)hexanoate (OP-lysine). The compound was synthesized independently from 3-hydroxypyridine and methyl 2-[(tert-butoxycarbonyl)amino]-6-iodohexanoate. The spectral and chromatographic properties of the synthetic OP-lysine and the substance isolated from hydrolyzed lenses were identical. HPLC analysis showed that the amounts of OP-lysine were higher in water-insoluble compared with water-soluble proteins and was higher in a pool of cataractous lenses compared with normal aged lenses, reaching 500 pmol/mg protein. The model incubations showed that an anaerobic reaction mixture of Nalpha-tert-butoxycarbonyllysine, glycolaldehyde, and glyceraldehyde could produce the Nalpha-t-butoxycarbonyl derivative of OP-lysine. The irradiation of OP-lysine with UVA under anaerobic conditions in the presence of ascorbate led to a photochemical bleaching of this compound. Our results argue that OP-lysine is a newly identified glycation product of lysine in the lens. It is a marker of aging and pathology of the lens, and its formation could be considered as a potential cataract risk-factor based on its concentration and its photochemical properties.

Topics: Aged; Aging; Ascorbic Acid; Caproates; Cataract; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Glycation End Products, Advanced; Humans; Hydrolysis; Lens, Crystalline; Light; Lysine; Magnetic Resonance Spectroscopy; Middle Aged; Models, Chemical; Pyridinium Compounds; Time Factors; Ultraviolet Rays; Water

Dietary caloric restriction (CR) is the only experimental intervention that can reliably retard the development of cataract in a normal animal model. Here we have studied the possible mechanisms by which CR retards the age-related degeneration of the lens of Brown Norway rats. We have found that CR slowed protein insolubilization and blunted declines of the total soluble thiols, protein thiols, reduced glutathione and ascorbic acid levels in the lenses of old BN rats. From the lens protein point of view, the development of cataract in rat lenses has 3 stages: (1) the precipitation of gamma-crystallin, (2) the insolubilization of beta-crystallin, and (3) the final precipitation of alpha-crystallin which was saturated with other denatured lens proteins. A similar sequence is also observed when the lens proteins are subjected to oxidative stress in vitro. These data are the first to suggest that CR may retard the age-related degeneration of the lens by attenuating the oxidative stress in the lens. Since oxidative stress is likely a main cause of human cataract, CR intervention may be relevant to humans as well.

Topics: Aging; Animals; Ascorbic Acid; Caloric Restriction; Cataract; Chromatography, High Pressure Liquid; Crystallins; Glutathione; Lens, Crystalline; Male; Oxidative Stress; Protein Denaturation; Rats; Rats, Inbred BN; Solubility; Sulfhydryl Compounds

The purpose of this study was to determine if high ascorbate of the human aqueous protects the lens against oxidative stress. Previous studies with the rat lens have been inconclusive because of its fortification with aldose reductase (AR), an important antioxidant. The human lens is deficient in this activity. These studies were hence done with the mouse lens, a species deficient in this enzyme. The reactive oxygen species (ROS)-induced physiological damage to the tissue was assessed in organ culture, by measuring its ability to actively transport 86Rb(+) ions, in the absence and presence of ascorbate. In addition, the status of tissue metabolism and its antioxidant reserve were assessed by quantitating ATP and glutathione (GSH). As expected, ROS decreased the membrane transport activity as well as the levels of ATP and GSH. Ascorbate minimized these toxic effects substantially. The presence of high ascorbate, therefore, appears highly beneficial in protecting the lens against oxidative damage and cataract formation, despite a deficiency of AR. The findings therefore appear to be significant from the point of view of using this nutrient for delaying the onset of cataract development in human beings, therapeutically as well as nutritionally.

Topics: Adenosine Triphosphate; Air; Aldehyde Reductase; Animals; Ascorbic Acid; Carbon Dioxide; Cataract; Glutathione; Lens, Crystalline; Mice; NADP; Oxidative Stress; Oxygen; Reactive Oxygen Species

Cataract is an important cause of blindness in dogs and frequently develops in young animals of certain breeds, such as the English cocker spaniel and the poodle. Protein oxidation is one of the mechanisms involved in lens opacification and may be causally related to depleted or diminished endogenous antioxidant defences. We evaluated the levels of enzymatic and nonenzymatic antioxidants in blood and aqueous humour of cataractous poodles in comparison to noncataractous poodles.. We studied 35 cataractous poodles aged 2 to 11 years, 14 noncataractous poodles and 15 noncataractous mixed-breed dogs. The activity of erythrocyte antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and glucose-6-phosphate dehydrogenase [G6PD]) was evaluated in 18 cataractous poodles and 14 noncataractous poodles. We evaluated ascorbic acid levels in plasma of all animals and in aqueous humour of cataractous poodles and mixed-breed dogs. The dogs were deprived of food for 12 hours before sampling. Blood samples were obtained from the jugular vein before and during anesthesia. Aqueous humour samples were obtained just before the anterior chamber was opened.. The activity of superoxide dismutase, G6PD and catalase was significantly higher in noncataractous poodles than in cataractous poodles (p < or = 0.05). The activity of glutathione peroxidase was lower in noncataractous poodles than in cataractous poodles, but not significantly so. There was no difference in mean plasma ascorbic acid concentration between cataractous poodles (21.3 microM [standard deviation (SD) 7.4 microM]), noncataractous poodles (21.6 microM [SD 7.4 microM]) and non-cataractous mixed-breed dogs (25.8 microM [SD 7.5 microM]). Similarly, there was no difference in mean aqueous humour ascorbic acid concentration between cataractous poodles (191.7 microM [SD 62.0 microM] and noncataractous mixed-breed dogs (215.7 microM [SD 91.8 microM]).. The results indicate that, at least in the population studied here, no correlation exists between the onset of cataract and ascorbic acid concentration in blood and aqueous humour. The decreased activity of antioxidant enzymes may explain in part the onset of cataract in poodles.

Topics: Animals; Antioxidants; Aqueous Humor; Ascorbic Acid; Catalase; Cataract; Cataract Extraction; Dog Diseases; Dogs; Erythrocyte Membrane; Glucosephosphate Dehydrogenase; Glutathione Peroxidase; Oxidative Stress; Oxidoreductases; Superoxide Dismutase

We examined whether short-term ascorbic acid deficiency impairs antioxidant status in the lens of guinea pigs. Male guinea pigs aged 4 wk were given a scorbutic diet (20 g/animal per day) with and without ascorbic acid (400 mg/animal per day) in drinking water for 3 wk. The ascorbic acid-deficient group showed no lens opacity. The ascorbic acid-deficient group had 14% of serum ascorbic acid concentration, 6% of aqueous humor ascorbic acid concentration, and 18% of lens ascorbic acid content in the ascorbic acid-adequate group. There were no differences in the contents of lens reduced glutathione and thiobarbituric acid reactive substances, an index of lipid peroxidation, between the ascorbic acid-deficient and adequate groups, while the deficient group had higher lens vitamin E content than the adequate group. The ascorbic acid-deficient group had higher serum vitamin E concentration than the ascorbic acid adequate group, while there were no differences in the concentrations of serum reduced glutathione and tiobarbituric acid reactive substances between the deficient and adequate groups. These results indicate that short-term ascorbic acid deficiency does not impair antioxidant status in the lens of guinea pigs despite induction of severe ascorbic acid depletion in the tissue, which may result in no cataract formation.

Topics: Animals; Antioxidants; Aqueous Humor; Ascorbic Acid; Ascorbic Acid Deficiency; Cataract; Diet; Glutathione; Guinea Pigs; Lens, Crystalline; Lipid Peroxidation; Male; Oxidation-Reduction; Thiobarbituric Acid Reactive Substances; Vitamin E

The authors investigated the concentrations of 8-isoprostaglandin F(2a), a marker of oxidative stress in vivo, and ascorbic acid, a protectant against oxidative damage, in the aqueous humour of patients with exfoliation syndrome (XFS) and cataract and compared the results with those in age matched patients with cataract, but without XFS, to determine whether XFS is associated with increased oxidative stress.. Aqueous humour was aspirated at the beginning of phacoemulsification cataract surgery from 27 eyes of 27 cataract patients with XFS and 27 eyes of 27 age matched cataract patients without XFS. 8-Isoprostaglandin F(2a)concentration in the aqueous was determined with a commercial immunoassay; ascorbic acid concentration was measured with a microplate assay method.. The mean concentration of 8-isoprostaglandin F(2a)in the aqueous from patients with XFS (2429 (SD 2940) pg/ml; range 400-10500 pg/ml) was significantly higher than that measured in the aqueous of age matched control patients (529.1 (226.8) pg/ml; range 325-1000 pg/ml); (p = 0.0028). Furthermore, mean ascorbic acid concentration in XFS patients (0.75 (0.39) mM; range 0.28-1.70 mM) was significantly lower than that found in control patients (1.19 (0.47) mM; range 0.53-2.4 mM); (p = 0.0005). There was a reverse correlation between 8-isoprostaglandin F(2a)and ascorbic acid concentration.. 8-Isoprostaglandin F(2a)was significantly increased in the aqueous of patients with XFS, and ascorbic acid was decreased, providing evidence of a role for free radical induced oxidative damage in the pathobiology of XFS.

Topics: Antioxidants; Aqueous Humor; Ascorbic Acid; Cataract; Dinoprost; Exfoliation Syndrome; F2-Isoprostanes; Free Radical Scavengers; Humans; Immunoassay; Oxidative Stress; Prospective Studies

Metabolomics, or metabolic profiling, is an emerging discipline geared to providing information on a large number of metabolites, as a complement to genomics and proteomics. In the current study, a fluorine-labeled derivative of ascorbic acid (F-ASA), a major antioxidant- and UV-trapping molecule in the aqueous humor and the lens, was used to investigate the extent to which the lens accumulates potentially toxic degradation products of vitamin C.. Human lens epithelial cells (HLE-B3) and rat lenses were exposed to hyperglycemic or oxidative stress in vitro or in vivo and probed for accumulation of F-ASA, fluoro-dehydroascorbate (F-DHA), fluoro-2,3-diketogulonate (F-DKG), and their degradation products in protein-free extracts, by proton-decoupled 750-MHz (19)F-nuclear magnetic resonance (NMR) spectroscopy.. F-ASA and F-DHA were taken up into HLE B-3 cells by an Na(+)-dependent transporter. Their uptake was unexpectedly only slightly affected by hyperglycemia in vitro, unless glutathione was severely depleted. Glycemic stress catalyzed oxidation of F-ASA into a single novel F-compound at -212.4 ppm, whereas F-DHA and F-DKG were the major degradation products observed after GSH depletion. In contrast, F-ASA uptake was markedly suppressed in diabetic cataractous rat lenses, which accumulated both the F-DHA and the -212.4-ppm compound. In an unexpected finding, the latter formed only from F-ASA and not F-DHA or F-DKG, suggesting a novel pathway of in vivo F-ASA degradation. Both the cells and the intact rat and human lenses were permeable to several advanced F-ASA and F-DHA degradation products, except F-DKG. The unknown compound at -212.4 ppm was the only F-ASA degradation product that spontaneously formed in rabbit aqueous humor upon incubation with F-ASA.. These studies suggest the existence of a novel ascorbic-acid-degradation pathway in the lens and aqueous humor that is influenced by the nature of the oxidant stress. Under similar culture conditions, intact lenses are more prone to hyperglycemia-mediated oxidant stress than are lens epithelial cells, but both are permeable to various F-ASA degradation products, the structure and biological roles of which remain to be established.

Topics: 2,3-Diketogulonic Acid; Adult; Aged; Animals; Ascorbic Acid; Biological Transport; Buthionine Sulfoximine; Cataract; Cell Culture Techniques; Cytochalasin B; Dehydroascorbic Acid; Enzyme Inhibitors; Epithelial Cells; Fluorine Radioisotopes; Galactose; Glucose; Glutathione; Humans; Hyperglycemia; Lens, Crystalline; Magnetic Resonance Spectroscopy; Male; Middle Aged; Organ Culture Techniques; Oxidative Stress; Rabbits; Rats; Rats, Sprague-Dawley

The development of cataracts in Atlantic salmon, Salmo salar L., was studied in 16 groups of smolts fed diets differing in prooxidant (iron, copper, manganese) and antioxidant (vitamin E, vitamin C, astaxanthin) composition and lipid level for 23 weeks in sea water, using a 2(7-3) reduced factorial design. The seven dietary variables were systematically varied at low (requirement level and 150 g lipid kg(-1)) and high levels (below known toxic levels and 320 g lipid kg(-1)). A mean endpoint cataract incidence of approximately 36% was observed. High dietary levels of vitamin C and astaxanthin reduced cataract frequency, whereas high dietary lipid level, iron and manganese were associated with increased cataract frequencies. Considering the nutritional status of selected organs of the fish, only the status of ascorbic acid correlated negatively to cataract development (P < 0.05). The lens glutathione (GSH) status was not correlated to cataract frequency, nor statistically explained by the dietary variables. However, the study shows that balancing the diet with respect to pro- and antioxidant nutrients may significantly protect Atlantic salmon against development of cataracts. An incidence of reversible osmotic cataract observed at week 14 was positively correlated to plasma glucose concentration.

Topics: Animals; Antioxidants; Aqueous Humor; Ascorbic Acid; beta Carotene; Blood Glucose; Cataract; Copper; Diet; Dietary Fats; Eye; Fish Diseases; Glucose; Glutathione; Incidence; Iron; Lipids; Manganese; Nutritional Status; Reactive Oxygen Species; Salmo salar; Vitamin E; Xanthophylls; Zinc

To investigate whether nutritional factors and possible risk factors for cataract influence the lens optical density (LOD).. Three hundred seventy-six subjects, aged 18 to 75 years, were recruited. In a cross-sectional design, serum was analyzed for lutein, zeaxanthin, vitamin C, alpha-tocopherol, and cholesterol levels. Adipose tissue (n = 187) was analyzed for lutein level. The LOD and the macular pigment optical density (MPOD) were measured by spectral fundus reflectance.. The mean +/- SD LOD at 420 nm was 0.52 +/- 0.17. It showed a significant association with age (beta =.008, P<001) and MPOD (beta = -.096, P =.02). For subjects 50 years and younger (mean +/- SD LOD, 0.45 +/- 0.11), we found only a single significant beta coefficient, for age (beta =.006, P<.001). For subjects older than 50 years (mean +/- SD LOD, 0.68 +/- 0.16), we found significant beta coefficients for age (beta =.011, P<.001) and MPOD (beta = -.240, P =.005). Controlling for age, we found no associations between LOD and other possible risk factors for age-related cataract or serum or adipose tissue concentrations of carotenoids, vitamin C, and alpha-tocopherol.. Macular pigment is composed of lutein and zeaxanthin, the only carotenoids found in human lenses. The inverse relationship between LOD and MPOD suggests that lutein and zeaxanthin may retard aging of the lens.

Topics: Adipose Tissue; Adolescent; Adult; Aged; Aging; alpha-Tocopherol; Ascorbic Acid; beta Carotene; Cataract; Cholesterol; Cross-Sectional Studies; Female; Humans; Lens, Crystalline; Lutein; Male; Middle Aged; Nutritional Status; Retinal Pigments; Risk Factors; Xanthophylls; Zeaxanthins

To investigate whether there is a role for ascorbic acid in the development of exfoliation syndrome (XFS).. A case-control study was undertaken that included consecutive patients with and without XFS in whom cataract surgery was indicated. Patients with ophthalmic conditions other than XFS and conditions that may influence ascorbic acid levels were excluded.. A prospective institutional study was undertaken. A small volume of aqueous humor was aspirated at the beginning of phacoemulsification cataract surgery. Eighty aqueous samples, 40 samples from 40 eyes of 40 cataract patients with XFS and 40 samples from 40 eyes of 40 age matched cataract patients without XFS, were collected and analyzed. Ascorbic acid concentration was evaluated in the aqueous samples with a microplate assay method.. The mean +/- SD concentration of ascorbic acid in the aqueous from patients with XFS (0.86 +/- 0.43 mM; range, 0.12 to 1.7 mM) was significantly lower than the concentration of ascorbic acid found in the aqueous of age-matched control patients (1.15 +/- 0.50 mM; range 0.42 to 3.1 mM; P =.0068). Total mean protein concentration was found to be significantly higher in the XFS group (481.1 +/- 196.8 pg/dl versus 336.3 +/- 86.4 pg/dl in the controls; P <.0001). Nevertheless, no correlation could be established between ascorbic level and protein concentration.. A significantly reduced mean level of ascorbic acid was observed in the aqueous humor of patients with XFS. In view of the fact that ascorbic acid is a major protective factor against free radical action, a role for free radical action is possible in the pathobiology of XFS.

Topics: Aged; Aqueous Humor; Ascorbic Acid; Case-Control Studies; Cataract; Exfoliation Syndrome; Humans; Phacoemulsification; Prospective Studies

Proper nutrition appears to protect against cataracts. Few studies have related nutrition to the odds of developing cortical or posterior subcapsular (PSC) cataracts.. We assessed the relation between usual nutrient intakes and age-related cortical and PSC lens opacities.. We studied 492 nondiabetic women aged 53-73 y from the Nurses' Health Study cohort who were without previously diagnosed cataracts. Usual nutrient intake was calculated as the average intake from 5 food-frequency questionnaires collected over a 13-15-y period before the eye examination. Duration of vitamin supplement use was determined from 7 questionnaires collected during this same period. We defined cortical opacities as grade > or = 0.5 and subcapsular opacities as grade > or =0.3 of the Lens Opacities Classification System III.. Some lenses had more than one opacity. No nutrient measure was related to prevalence of opacities in the full sample, but significant interactions were seen between age and vitamin C intake (P = 0.02) for odds of cortical opacities and between smoking status and folate (P = 0.02), alpha-carotene (P = 0.02), beta-carotene (P = 0.005), and total carotenoids (P = 0.02) for odds of PSC opacities. For women aged <60 y, a vitamin C intake > or = 362 mg/d was associated with a 57% lower odds ratio (0.43; 95% CI: 0.2, 0.93) of developing a cortical cataract than was an intake <140 mg/d, and use of vitamin C supplements for > or = 10 y was associated with a 60% lower odds ratio (0.40; 0.18, 0.87) than was no vitamin C supplement use. Prevalence of PSC opacities was related to total carotenoid intake in women who never smoked (P = 0.02).. Our results support a role for vitamin C in diminishing the risk of cortical cataracts in women aged <60 y and for carotenoids in diminishing the risk of PSC cataracts in women who have never smoked.

Topics: Age Factors; Aged; Aging; Antioxidants; Ascorbic Acid; Carotenoids; Cataract; Cohort Studies; Diet Surveys; Dietary Supplements; Female; Humans; Lens Nucleus, Crystalline; Longitudinal Studies; Middle Aged; Nutrition Assessment; Odds Ratio; Prevalence; Prospective Studies; Smoking; Surveys and Questionnaires; United States; Vitamins; Women's Health

The protein-bound chromophores, which increase with aging in the human lens, act as UVA sensitizers, producing almost exclusively singlet oxygen in vitro. Direct irradiation of whole, aged human lenses with high intensity UVA light (200 mW cm(-2) for 24 hr), however, failed to produce singlet oxygen damage, as evidenced by the lack of either His or Trp photodestruction. Total homogenates of human lenses prepared in a cuvette under air did show destruction of His and Trp residues by UVA light, but no destruction was seen when equivalent homogenates were prepared under argon. These data are consistent with the idea that the low oxygen levels in the lens prevent singlet oxygen damage in vivo.UVA irradiation of aged human lenses in culture caused an extensive photobleaching of the yellow chromophores. A time course indicated that the photobleaching increased with time, with significant color loss apparent after 6 hr. Homogenization of the irradiated and dark control lenses in 6 M guanidine-HCl, followed by determination of the difference spectrum, showed approximately 50% bleaching of compounds with a lambda(max) at 355 nm. Similarly, fluorophores with a lambda(max) for excitation of 355 nm and for emission of 420 nm were 50% destroyed by the UVA light. Similar results were obtained in vitro by the anaerobic irradiation of a sonication-solubilized WI fraction from type II brunescent cataracts and from aged human lenses. In this system, there was an initial bleaching of 15% after 30 min of irradiation, followed by a slow increase over the next 6 hr to a final bleaching of 30%. The addition of 1.0 m M ascorbic acid, but not 1.0 m M glutathione (GSH), increased the photobleaching to 60% under argon, and the loss of ascorbate could be detected under these anaerobic conditions. In the presence of air, UVA light produced no photobleaching, but rather caused a three-fold increase in absorbance at 345 nm, which was prevented by the inclusion of 1.0 m M ascorbic acid and almost 50% inhibited by 1.0 m M GSH. The data are consistent with the conversion of the triplet state of the sensitizers to anion and cation radicals in the absence of oxygen. Photobleaching may occur either by dismutation of the anion radical or by reduction of the anion radical by ascorbate via type I chemistry. UVA irradiation of an enriched fraction of sensitizers from a proteolytic digest from type II cataract lenses produced a 63% bleaching at 330 nm in the absence of oxygen, and the almost comp

Topics: Aged; Ascorbic Acid; Cataract; Chromatography, High Pressure Liquid; Culture Techniques; Humans; Lens, Crystalline; Middle Aged; Oxygen; Pigments, Biological; Ultraviolet Rays

Topics: Age Factors; Ascorbic Acid; Cataract; Female; Humans; Reference Values

Cataract is an important visual problem of older people and a substantial health care cost in many countries. Most studies investigating risk factors for cataract have been conducted in the United States, and there is less information on the possible role of dietary factors in European populations. We conducted a case-control study to investigate the association of antioxidant vitamins (vitamin C, vitamin E, vitamin A, beta-carotene, alpha-carotene, beta-cryptoxanthin, lycopene, zeaxanthin and lutein) and minerals (zinc and selenium) and risk of cataract in a Mediterranean population. Cases with cataract (343) and 334 age/sex frequency-matched controls aged 55 to 74 y were selected from an ophthalmic outreach clinic in Valencia, Spain. Participants were interviewed about their diet using a Food Frequency Questionnaire, and other information on potential confounders, such as smoking, alcohol, and education. Blood samples were analyzed by a colorimetric method for vitamin C and by reversed-phase HLPC for other blood antioxidants. Blood levels of vitamin C above 49 micromol/L were associated with a 64% reduced odds for cataract (P < 0.0001). Dietary intake of vitamins C, E and selenium were marginally associated with decreased odds (P = 0.09, P = 0.09, P = 0.07, respectively), whereas moderately high levels of blood lycopene (>0.30 micromol/L) were associated with a 46% increased odds of cataract (P = 0.04). Our results strengthen the evidence for a protective role for vitamin C on the aging lens as this effect was seen in a population characterized by high vitamin C intakes.

Topics: Aged; Aging; Alcohol Drinking; Antioxidants; Ascorbic Acid; Case-Control Studies; Cataract; Chromatography, High Pressure Liquid; Colorimetry; Diet Surveys; Educational Status; Female; Humans; Male; Middle Aged; Minerals; Odds Ratio; Risk Factors; Smoking; Spain; Surveys and Questionnaires; Vitamins

In 1992 Radlmaier showed that catalase can protect bovine lens epithelial cultures from blue light. The following experiments have the aim to examine, if vitamin C and E have protective functions, also.. 367 cultures of bovine lens epithelial cells were incubated in Medium 199 added by 20% foetal calf serum FCS, by 125 I.U./ml penicillin, by 125 mg/ml Streptomycin, by 0.31 microgram/ml amphotericin B, by 2% L-Glutamin (200 mM), and by 1.25% Hepesbuffer. The incubation temperature was kept at 36 degrees C at a pCO2 of 5%. In order to avoid secondary morphologic alterations, we experimented only on the second to the third subculture. Light exposure followed three days after addition of the substances such as Cebion 500 (R) ad injection (6 mg/dl) and E-Vicotrat (R) ad injection (0.5 mg/dl). The blue light (420-430 nm, Draeger) was applied in a baby bed at 36 degrees C for four hours (1.1 mW/cm). The UV-A lamp was constructed and described by Heller [7]; at a wave length of 300-400 nm, the irradiation time was 10 minutes at 100 mW/cm2. In morphologic evaluation we looked for criteria such as cell diameter, cellular wall alterations, cellular inclusions and vacuoles. The cell count was done after staining with the vital dye trypan-blue in Neubauer's chamber. In statistic evaluation we used the pair comparison of Tuckey and Kruskall-Wallis-Test.. After addition of 0.5 mg/ml vitamin E: In 89 cultures, morphologic evaluation and cell count showed a significant protection against light toxicity: After Uv-A-irradiation we counted 50% more living cells and after blue light 30% more. After addition of 6 mg/ml Cebion vitamin C: Morphologic evaluation and cell count of 223 cultures showed them also to be significantly protected: after irradiation by UV-A we counted 25% more and after exposition to blue light 15% more living cells.. The demonstrated experiments significantly showed, that vitamin C and vitamin E can protect lens epithelial cultures from toxic stress by blue and by UV-A light and might delay cataract formation in man.

Topics: Animals; Antioxidants; Ascorbic Acid; Cataract; Cattle; Cell Count; Cells, Cultured; Epithelial Cells; Lens, Crystalline; Light; Ultraviolet Rays; Vitamin E

To determine whether the human lens contains argpyrimidine, a modification of arginine by methylglyoxal, to establish how argpyrimidine content relates to lens aging and cataract formation.. A monoclonal antibody was used to measure argpyrimidine by a competitive ELISA in water soluble (WS) and insoluble (WI) lens fractions from young, aged, nuclear cataractous, and brunescent cataractous lenses. Brunescent cataractous lens proteins were digested by enzymes, the digest was subjected to HPLC, and the eluate was analyzed for argpyrimidine. Lens proteins from aged lenses (from donors 65 to 80 years of age) were fractionated on a Sephadex G-200 column, and the crystallins were tested for argpyrimidine.. The competitive ELISA showed two to three times as much argpyrimidine in water-insoluble proteins as in water-soluble proteins. Although no clear cut increase with the age of the lens donors in either the water-soluble or the insoluble protein fractions was found, the argpyrimidine levels in brunescent cataractous lenses were significantly higher (254.0 +/- 155 pmol/mg protein, P < 0.005) than in age-matched, aged (16.1 +/- 8 pmol/mg) or nuclear cataractous lenses (49.0 +/- 26 pmol/mg). Lenses from diabetic individuals showed a modest increase (50.3 pmol/mg) compared with age-matched normal lenses. HPLC results provided additional evidence that human lenses contain argpyrimidine. Western blotting experiments showed consistently stronger reactions with cataractous lens proteins than those from noncataractous lenses, and argpyrimidine was found in both crystallin monomers and polymers. All crystallins and several cross-linked high-molecular-weight aggregates reacted with the antibody to argpyrimidine, but a protein of approximately 28 kDa in the alpha-crystallin fraction displayed the greatest immunoreactivity.. Methylglyoxal modifies arginine within the human lens, and the changes occur at a much higher rate in brunescent lens proteins than in either nuclear cataractous or normal lenses. All crystallins contained argpyrimidine and covalently cross-linked aggregates. This is the first report of immunologic evidence for an arginine modification in the human lens by a physiologically important alpha-dicarbonyl compound.

Topics: Adolescent; Aged; Aged, 80 and over; Aging; Antibodies, Monoclonal; Ascorbic Acid; Blotting, Western; Carbohydrate Metabolism; Cataract; Chromatography, High Pressure Liquid; Crystallins; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Humans; Lens, Crystalline; Maillard Reaction; Ornithine; Pyrimidines

We examined the effect of prolonged marginal ascorbic acid deficiency of the levels of antioxidants and lipid peroxide in lenses of guinea pigs in order to clarify lenticular antioxidant status under ascorbic acid deficiency. Male guinea pigs aged 4 weeks were given a scorbutic diet (20 g/animal per day) with either marginally deficient ascorbic acid (0.5 mg/animal per day) or sufficient ascorbic acid (1 g/animal per day) in drinking water for 3 and 6 months. The deficient group showed no lens opacity during the administration period. The deficient group had 62.3 and 53.9% of lenticular ascorbic acid content in the sufficient group at 3 and 6 months of ascorbic acid deficiency, respectively. There were no differences in lenticular contents of reduced glutathione and thiobarbituric acid reactive substances, an index of lipid peroxidation, between both groups at 3 and 6 months of ascorbic acid deficiency, while the deficient group tended to have higher lenticular vitamin E content than the sufficient group. The deficient group had higher serum vitamin E concentration than the sufficient group at 3 and 6 months of ascorbic acid deficiency. These results indicate that lenticular antioxidant status is maintained well in guinea pigs with prolonged marginal ascorbic acid deficiency, which may result in no cataract formation.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cataract; Glutathione; Guinea Pigs; Lens, Crystalline; Lipid Peroxidation; Male; Nutritional Status; Thiobarbituric Acid Reactive Substances; Vitamin E

To assess the relation between usual nutrient intake and subsequently diagnosed age-related nuclear lens opacities.. Four hundred seventy-eight nondiabetic women aged 53 to 73 years from the Boston, Mass, area without previously diagnosed cataracts sampled from the Nurses' Health Study cohort.. Usual nutrient intake was calculated as the average intake from 5 food frequency questionnaires that were collected during a 13- to 15-year period before the evaluation of lens opacities. The duration of vitamin supplement use was determined from 7 questionnaires collected during this same period. We defined nuclear opacities as a nuclear opalescence grade of 2.5 or higher using the Lens Opacification Classification System III.. The prevalence of nuclear opacification was significantly lower in the highest nutrient intake quintile category relative to the lowest quintile category for vitamin C (P<.001), vitamin E (P =.02), riboflavin (P =.005), folate (P =.009), beta-carotene (P =.04), and lutein/zeaxanthin (P =.03). After adjustment for other nutrients, only vitamin C intake remained significantly associated (P =.003 for trend) with the prevalence of nuclear opacities. The prevalence of nuclear opacities was significantly lower (P<.001) in the highest vitamin C intake quintile category relative to the lowest quintile category (odds ratio, 0.31; 95% confidence interval, 0.16-0.58). There were also statistically significant trends of decreasing prevalence of nuclear opacities with increasing duration of use of vitamin C (P =.004 for trend), vitamin E (P =.03 for trend), and multivitamin (P =.04 for trend) supplements, but only duration of vitamin C supplement use remained significantly associated with nuclear opacities after mutual adjustment for use of vitamin E (P =.05 for trend) or multivitamin (P =.02 for trend) supplements. The prevalence of nuclear opacities was significantly lower (P =.004) for women who used a vitamin C supplement for 10 or more years relative to women who never used vitamin C supplements (odds ratio, 0.36; 95% confidence interval, 0.18-0.72). Plasma measures of vitamins C and E taken at the eye examination were also inversely associated with the prevalence of nuclear opacities.. These results provide additional evidence that antioxidant nutrients play a role in the prevention of age-related nuclear lens opacities.

Topics: Aged; Aging; Antioxidants; Ascorbic Acid; beta Carotene; Cataract; Cohort Studies; Diet Records; Diet Surveys; Feeding Behavior; Female; Folic Acid; Humans; Lens Nucleus, Crystalline; Lutein; Middle Aged; Odds Ratio; Prevalence; Riboflavin; Vitamin E; Women's Health; Xanthophylls; Zeaxanthins

Chromatographic evidence supporting the similarity of the yellow chromophores isolated from aged human and brunescent cataract lenses and calf lens proteins ascorbylated in vitro is presented. The water-insoluble fraction from early stage brunescent cataract lenses was solubilized by sonication (WISS) and digested with a battery of proteolytic enzymes under argon to prevent oxidation. Also, calf lens proteins were incubated with ascorbic acid for 4 weeks in air and submitted to the same digestion. The percent hydrolysis of the proteins to amino acids was approximately 90% in every case. The content of yellow chromophores was 90, 130 and 250 A(330) units/g protein for normal human WISS, cataract WISS and ascorbate-modified bovine lens proteins respectively. Aliquots equivalent to 2.0 g of digested protein were subjected to size-exclusion chromatography on a Bio-Gel P-2 column. Six peaks were obtained for both preparations and pooled. Side by side thin-layer chromatography (TLC) of each peak showed very similar R(f) values for the long wavelength-absorbing fluorophores. Glycation with [U-(14)C]ascorbic acid, followed by digestion and Bio-Gel P-2 chromatography, showed that the incorporated radioactivity co-eluted with the A(330)-absorbing peaks, and that most of the fluorescent bands were labeled after TLC. Peaks 2 and 3 from the P-2 were further fractionated by preparative Prodigy C-18 reversed-phase high-performance liquid chromatography. Two major A(330)-absorbing peaks were seen in peak 2 isolated from human cataract lenses and 5 peaks in fraction 3, all of which eluted at the same retention times as those from ascorbic acid glycated calf lens proteins. HPLC fractionation of P-2 peaks 4, 5 and 6 showed many A(330)-absorbing peaks from the cataract WISS, only some of which were identical to the asorbylated proteins. The major fluorophores, however, were present in both preparations. These data provide new evidence to support the hypothesis that the yellow chromophores in brunescent lenses represent advanced glycation endproducts (AGEs) probably due to ascorbic acid glycation in vivo.

Topics: Animals; Ascorbic Acid; Carbon Radioisotopes; Cataract; Cattle; Chromatography, Gel; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Crystallins; Glycation End Products, Advanced; Glycosylation; Humans; Peptide Hydrolases

To investigate the relationships between plasma concentrations of antioxidant vitamins and carotenoids and nuclear, cortical, and posterior subcapsular cataracts in a group of elderly men and women.. Cross-sectional survey.. Three hundred seventy-two men and women, aged 66 to 75 years, born and still living in Sheffield, England.. The Lens Opacities Classification System (LOCS) III was used to grade nuclear, cortical, and posterior subcapsular lens opacities. Fasting blood samples were taken to assess plasma concentrations of vitamin C, vitamin E, alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin.. Logistic regression analyses of the associations between plasma vitamin concentrations and cataract subtype, adjusting for age, gender, and other risk factors.. After adjustment for age, gender, and other risk factors, risk of nuclear cataract was lowest in people with the highest plasma concentrations of alpha-carotene (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.3-0.9, P for trend 0.006) or beta-carotene (OR, 0.7; 95% CI, 0.4-1.4, P for trend 0.033). Risk of cortical cataract was lowest in people with the highest plasma concentrations of lycopene (OR, 0.4; 95% CI, 0.2-0.8, P for trend 0.003), and risk of posterior subcapsular cataract was lowest in those with higher concentrations of lutein (OR, 0.5; 95% CI, 0.2-1.0, P for trend 0.012). High plasma concentrations of vitamin C, vitamin E, or the carotenoids zeaxanthin and beta-cryptoxanthin were not associated with decreased risk.. These findings suggest that a diet rich in carotenoids may protect against cataract development, but because they are based on observational data, they need to be confirmed in randomized controlled trials.

Topics: Aged; Aging; Antioxidants; Ascorbic Acid; Carotenoids; Cataract; Cross-Sectional Studies; England; Female; Humans; Male; Odds Ratio; Risk Factors; Vitamin E

Recent studies have identified specific hydroxylated amino acid oxidation products which strongly suggest the presence of hydroxyl radical (HO.)-damaged proteins in human cataractous lenses. In the present study, the ability of early stage (type II) and advanced (type IV) nuclear cataractous lens homogenates to catalyse HO. production in the presence of H(2)O(2)was investigated using electron paramagnetic resonance (EPR) spectroscopy with the free radical trap, 5,5-dimethyl-1-pyrroline- N -oxide (DMPO). Cataractous lens homogenates incubated with 1 m m H(2)O(2)generated a distinct HO. signal, which was significantly more intense in the nuclear region of the type IV compared to the type II lenses. The ability of individual lens nuclei and cortices to stimulate HO. production was positively correlated. The DMPO-HO. signal was competitively inhibited by ethanol, confirming that the DMPO-HO. signal was due to HO. formation and not DMPO-OOH degradation. The metal ion chelator, diethylenetriaminepentaacetic acid, also inhibited HO. formation, indicating that lenticular metal ions play a key role in HO. formation. Cataractous lens homogenates also stimulated ascorbyl radical production, further suggesting the presence of redox-active metal ions in the tissue. Analysis of lenses for total Fe and Cu (using atomic absorption spectrometry) showed that the more advanced type IV lenses tended to have higher Fe, but similar Cu, levels compared to the type II lenses. The levels of both metals were lower in non-cataractous lenses. These data support the hypothesis that transition metal-mediated HO. production may play a role in the aetiology of age-related nuclear cataract.

Topics: Ascorbic Acid; Cataract; Copper; Humans; Hydrogen Peroxide; Hydroxyl Radical; Iron; Lens, Crystalline; Oxidation-Reduction; Spectrophotometry, Atomic

With age, human lens crystallins become more pigmented, oxidized, modified by ascorbate oxidation and advanced glycation end products (AGEs), and bind copper. The hypothesis was tested that the major AGE and ascorbylation product in the human lens, N(epsilon)-carboxymethyl-L-lysine (CML), has an EDTA-like structure, which may predispose it to bind redox active copper.. Young, old, and cataractous human lens protein fractions were glycated with ascorbic acid and tested for their ability to bind Cu(II) by atomic absorption spectroscopy and oxidize (14C1)-ascorbate by radiometric thin-layer chromatography method. AGEs were assayed by high-performance liquid chromatography (HPLC). CML-rich proteins were immunoprecipitated from young, old, and cataractous crystallins using affinity-purified CML antibody and tested for their ability to oxidize ascorbate and generate hydroxyl radicals in the presence of H2O2 using 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) spin-trap and EPR spectroscopy.. Ascorbate oxidizing activity at 24 hours of native crystallins was significantly increased in both the water soluble (WS; P < 0.001) and insoluble (WIS; P < 0.05) fractions from cataractous and normal lenses. The chelator DTPA completely prevented oxidation up to 24 hours of incubation but less effectively thereafter. Mean endogenous Cu content in pooled young, old, and cataract fractions increased from 0.016 to 0.026 nmol/mg protein, respectively, in WS (P < 0.05) and WIS (P < 0.001) fractions, and Cu(II) binding was 20% to 30% increased in cataractous versus old and young lenses in WS (P < 0.01) and WIS (P < 0.001) fractions. Mean levels of the AGEs, CML, and pentosidine were markedly elevated in WS and WIS fractions from cataractous versus old or young crystallins (20% to severalfold, P < 0.05 to P < 0.001). In a separate experiment, protein-bound Fe was not elevated. Crystallins ascorbylated in vitro showed an increase in CML as well as Cu(II) binding. CML-rich proteins (immunoprecipitated from cataractous lenses) oxidized ascorbate approximately 4 times faster than similar proteins from young and old normal lenses (P < 0.01) and generated hydroxyl radicals in the presence of H2O2 and DMPO.. The association between CML formation, copper binding, and generation of free radicals by cataractous lens crystallins can be duplicated by ascorbylation in vitro. These effects are only in part attributable to CML itself, and other modifications (AGEs, conformational changes) may participate in the process. A vicious cycle between AGE formation, lipoxidation, and metal binding may exist in the aging lens, suggesting that chelation therapy could be beneficial in delaying cataractogenesis.

Topics: Ascorbic Acid; Cataract; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Copper; Crystallins; Electron Spin Resonance Spectroscopy; Glycation End Products, Advanced; Glycosylation; Humans; Lens, Crystalline; Lysine; Oxidation-Reduction; Spectrophotometry, Atomic

The kynurenine pathway catabolite 3-hydroxykynurenine (3HK) and redox-active metals such as copper and iron are implicated in cataractogenesis. Here we investigate the reaction of kynurenine pathway catabolites with copper and iron, as well as interactions with the major lenticular structural proteins, the alpha-crystallins. The o-aminophenol kynurenine catabolites 3HK and 3-hydroxyanthranilic acid (3HAA) reduced Cu(II)>Fe(III) to Cu(I) and Fe(II), respectively, whereas quinolinic acid and the nonphenolic kynurenine catabolites kynurenine and anthranilic acid did not reduce either metal. Both 3HK and 3HAA generated superoxide and hydrogen peroxide in a copper-dependent manner. In addition, 3HK and 3HAA fostered copper-dependent alpha-crystallin cross-linking. 3HK- or 3HAA-modifed alpha-crystallin showed enhanced redox activity in comparison to unmodified alpha-crystallin or ascorbate-modified alpha-crystallin. These data support the possibility that 3HK and 3HAA may be cofactors in the oxidative damage of proteins, such as alpha-crystallin, through interactions with redox-active metals and especially copper. These findings may have relevance for understanding cataractogenesis and other degenerative conditions in which the kynurenine pathway is activated.

Topics: 3-Hydroxyanthranilic Acid; Animals; Ascorbic Acid; Cataract; Cattle; Copper; Crystallins; Electrochemistry; Humans; Hydrogen Peroxide; Iron; Kynurenine; Lens, Crystalline; Metals; Oxidation-Reduction; Superoxides; Tryptophan

The interaction of hydrogen peroxide, ascorbate and microperoxidase-11 (MP11), a ferriheme undecapeptide derived from cytochrome c, has been investigated using spectrophotometry, oxymetry, electron paramagnetic resonance (EPR), and mass spectroscopy techniques. It is shown that in 50 m M phosphate pH 7. 0-7.4 in the absence of other reactants H(2)O(2)induces a concentration-dependent decrease in absorption at the Soret band (399 nm) of the microperoxidase, with concomitant H(2)O(2)decomposition and oxygen evolution. The reaction causes irreversible heme degradation, concomitant with loss of enzymatic activity. Ascorbate effectively protects MP11 from degradation and inhibits oxygen evolution. At ascorbate concentrations greater than that of H(2)O(2), microperoxidase degradation is almost completely prevented. Mass spectrometry showed that H(2)O(2)oxidizes the microperoxidase to a monooxygenated product, which did not form if ascorbate was included in the reaction system. There appears to be a 1:1 relationship between H(2)O(2)degradation and ascorbate oxidation. EPR experiments revealed that an ascorbate radical was formed during the reaction. These reactions may be described by a scheme where a putative 'compound I' of the microperoxidase is reduced by ascorbate back to the original redox state (ferric) of the peroxidase in two one-electron steps, concomitantly with oxidation of the ascorbate to an ascorbate radical or in one two-electron transfer step forming dehydroascorbate. In the absence of ascorbate, the 'compound I' reacts further with the peroxide causing microperoxidase degradation and partial oxygen evolution. These observations are relevant to the interaction of ferrihemes with H(2)O(2)and ascorbic acid and may be pertinent for the potential application of MP11 as an anti-cataract agent.

Topics: Ascorbic Acid; Cataract; Drug Interactions; Electron Spin Resonance Spectroscopy; Humans; Hydrogen Peroxide; Mass Spectrometry; Oxidation-Reduction; Oxygen; Peroxidases

To determine the relationship between vitamin supplement use and the 5-year incidence of nuclear, cortical, and posterior subcapsular cataract in the Beaver Dam Eye Study cohort.. The 5-year incidence of cataract, determined from slitlamp (nuclear cataract) and retroillumination (cortical and posterior subcapsular cataract) photographs, was assessed in a population-based cohort of persons participating in baseline (1988-1990) and follow-up (1993-1995) examinations. Detailed data regarding the type, dosage, and duration of supplement use were obtained by in-person interviews at follow-up.. Residents of Beaver Dam, Wis, aged 43 to 86 years, were identified by private census. Of the 3684 participants in both baseline and follow-up examinations, 3089 were eligible for incident cataract analysis in the present study.. Compared with nonusers, the 5-year risk for any cataract was 60% lower among persons who, at follow-up, reported the use of multivitamins or any supplement containing vitamin C or E for more than 10 years. Taking multivitamins for this duration lowered the risk for nuclear and cortical cataracts but not for posterior subcapsular cataracts (odds ratios [95% confidence intervals] = 0.6 [0.4-0.9], 0.4 [0.2-0.8], and 0.9 [0.5-1.9], respectively). Use of supplements for shorter periods was not associated with reduced risk for cataract. Measured differences in lifestyle between supplement users and nonusers did not influence these associations, nor did variations in diet as measured in a random subsample.. These data add to a body of evidence suggesting lower risk for cataract among users of vitamin supplements and stronger associations with long-term use. However, the specific nutrients that are responsible cannot be ascertained at this time, and unmeasured lifestyle differences between supplement users and nonusers may explain these results. Arch Ophthalmol. 2000;118:1556-1563

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Cataract; Dietary Supplements; Female; Humans; Incidence; Lens, Crystalline; Male; Middle Aged; Nutrition Surveys; Risk Factors; Vitamin E; Wisconsin

There is strong evidence to show that diabetes is associated with increased oxidative stress. However, the source of this oxidative stress remains unclear. Using transgenic mice that overexpress aldose reductase (AR) in their lenses, we found that the flux of glucose through the polyol pathway is the major cause of hyperglycemic oxidative stress in this tissue. The substantial decrease in the level of reduced glutathione (GSH) with concomitant rise in the level of lipid peroxidation product malondialdehyde (MDA) in the lens of transgenic mice, but not in the nontransgenic mice, suggests that glucose autoxidation and nonenzymatic glycation do not contribute significantly to oxidative stress in diabetic lenses. AR reduction of glucose to sorbitol probably contributes to oxidative stress by depleting its cofactor NADPH, which is also required for the regeneration of GSH. Sorbitol dehydrogenase, the second enzyme in the polyol pathway that converts sorbitol to fructose, also contributes to oxidative stress, most likely because depletion of its cofactor NAD+ leads to more glucose being channeled through the polyol pathway. Despite a more than 100% increase of MDA, oxidative stress plays only a minor role in the development of cataract in this acute diabetic cataract model. However, chronic oxidative stress generated by the polyol pathway is likely to be an important contributing factor in the slow-developing diabetic cataract as well as in the development of other diabetic complications.--Lee, A. Y. W., Chung, S. S. M. Contributions of polyol pathway to oxidative stress in diabetic cataract. FASEB J. 13, 23-30 (1999)

Topics: Aldehyde Reductase; Animals; Antioxidants; Ascorbic Acid; Buthionine Sulfoximine; Cataract; Culture Media; Diabetes Mellitus, Experimental; Enzyme Inhibitors; Gene Expression; Glutathione; Glyceraldehyde; L-Iditol 2-Dehydrogenase; Lens, Crystalline; Malondialdehyde; Mice; Mice, Transgenic; Organ Culture Techniques; Oxidative Stress; Polymers; Vitamin E

Cataractous lenses have been found to have an altered distribution of the intracellular ionic environment: the concentrations of potassium and magnesium being decreased and the concentrations of sodium and calcium increased. These changes arise as a result of changes to lens membrane characteristics causing an increase in lens membrane permeability. In this study flame atomic absorption spectroscopy (AAS) was used for calcium, magnesium, iron and zinc determination, and flame atomic emission spectroscopy (AES) was used for sodium and potassium contents in normal and cigarette smoke-exposed rat lenses. The methods are sensitive enough to detect quantitatively all six cations in a single rat lenses. In this work, six elements, including Ca2+, K+, Na+, Zn2+, Fe2+ and Mg2+ in experimental rat eye lenses and normal transparent lenses were determined. It was found that the concentrations of Ca2+, Na+, Zn2+, and Fe2+ were increased dramatically while K+ and Mg2+ decreased in smoke-exposed rat lenses when compared to the control rat lenses. There were no significant changes between 'smoked' rats supplied with vitamin C and control groups. A positive correlation was found also in the other two groups of 'cigarette smoked' animals supplemented with selenium plus vitamin E and selenium when compared with 'cigarette smoked' without any supplements. These data provide support for the hypothesis that cigarette smoking increases the risk of cataract formation. We investigated whether vitamin C is the most important antioxidant in the body. The roles of diet with optimum amounts of antioxidant vitamins C and vitamin E and the antioxidant mineral selenium are discussed.

Topics: Animals; Antioxidants; Ascorbic Acid; Calcium; Cataract; Iron; Lens, Crystalline; Magnesium; Micronutrients; Oxidative Stress; Potassium; Rats; Rats, Wistar; Selenium; Smoking; Sodium; Spectrophotometry, Atomic; Vitamin E; Zinc

Carbohydrates with reactive aldehyde and ketone groups can undergo Maillard reactions with proteins to form advanced glycation end products. Oxalate monoalkylamide was identified as one of the advanced glycation end products formed from the Maillard reaction of ascorbate with proteins. In these experiments, we have analyzed human lens proteins immunochemically for the presence of oxalate monoalkylamide. Oxalate monoalkylamide was absent in most of the very young lenses but was present in old and cataractous lenses. The highest levels were found in senile brunescent lenses. Incubation experiments using bovine lens proteins revealed that oxalate monoalkylamide could form from the ascorbate degradation products, 2,3-diketogulonate and L-threose. These data provide the first evidence for oxalate monoalkylamide in vivo and suggest that ascorbate degradation and its binding to proteins are enhanced during lens aging and cataract formation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Alkanes; Amides; Animals; Antibody Specificity; Ascorbic Acid; Cataract; Cattle; Child; Crystallins; Glycation End Products, Advanced; Humans; Lens, Crystalline; Maillard Reaction; Middle Aged; Oxalates

The proteins isolated from aged human lenses and brunescent cataracts exhibit extensive disulfide bond formation. Diabetic rat lenses similarly contain disulfide-bonded protein aggregates. These observations are consistent with the known link between diabetes, glycation and oxidative damage, and suggest a role for reactive oxygen species (ROS) in this process. To assess whether the glycation-related modifications in human lens proteins spontaneously generate ROS, superoxide anion formation was measured using both cataractous lens proteins and calf lens proteins glycated in vitro with ascorbic acid (ascorbylated). The water-insoluble fraction from aged normal human lenses generated 0.3-0.6 nmol superoxide h(-1)mg protein(-1), whereas the activity increased to 0.5-1.8 nmol h(-1)mg protein(-1)with the WI fraction from brunescent cataracts, and 2.3 nmol h(-1)mg protein(-1)with calf lens proteins ascorbylated for 4 weeks in vitro. The activity in the human lens proteins was observed in both the water-soluble and water-insoluble fractions, and was completely dependent upon the presence of oxygen. The pH optimum curve for superoxide formation increased from pH 6.5 to 10 with both the cataract and ascorbylated proteins. The superoxide-generating activity in human lens was completely bound to a boronate affinity column, but only partially bound with the ascorbylated proteins. The superoxide anion produced by a 5 m m solution of purified N(epsilon)-fructosyl-lysine was barely detectable, and therefore, could not account for the superoxide formed by any of the lens protein preparations. Also, superoxide formation increased 10-fold at pH 8.8 with fructosyl-lysine, but only 1.3-1.8-fold with human lens proteins. The addition of copper-stimulated superoxide formation with glycated bovine serum albumin, but no stimulation was seen with cataractous proteins. Assays of specific compounds showed that catechol, hydroquinone, 3-OH kynurenine and 3-OH anthranylic acid exhibited the greatest activity for superoxide generation, but had a very short halflife. 2,3-Dihydroxypyridine and 4,5 dihydroxynaphthalene were one and two orders of magnitude less reactive. In long-term incubations at 37 degrees, cataractous proteins retained the potential to produce superoxide anion, losing only half of the initial activity after 6-7 days. Therefore, the water-insoluble fraction from aged human lenses and dark brown cataracts are potentially capable of generating >100 nmol mg protein(-1)and

Topics: Aged; Aged, 80 and over; Animals; Anions; Ascorbic Acid; Cataract; Cattle; Chromatography, Affinity; Crystallins; Humans; Reactive Oxygen Species; Superoxides

The water-insoluble (WI) fraction from aged human lenses contains yellow chromophoric sensitizers, which generate reactive oxygen species (ROS) when irradiated with UVA light. The WI proteins from type I to V brunescent cataract lenses were assayed for UVA-dependent superoxide anion synthesis. Rates varied from 8.4-15 nMol h(-1)mg protein(-1), but there was no significant difference in specific activity between cataract types. When calf lens soluble proteins were incubated with ascorbic acid for 4 weeks and dialyzed, they were capable of generating 30-40 nMol h(-1)mg protein(-1)superoxide anion when irradiated with UVA light. Two preparations each of brunescent cataract WI proteins and bovine lens proteins ascorbylated in vitro were extensively digested with proteolytic enzymes and the released amino acids separated by normal phase HPLC. The elution profiles of the digests were very similar based upon the absorbance at 330 nm and fluorescence at 350 nm excitation/450 nm emission. Each peak was pooled and analyzed for the UVA-dependent generation of both superoxide anion and singlet oxygen. Every peak exhibited sensitizer activity, and the UVA-dependent ROS generation was roughly proportional to the absorbance at 330 nm. In addition, the ratio of superoxide anion to singlet oxygen generated was similar with both preparations. These data argue that it is the brown, fluorescent compounds which accumulate during aging and cataract formation that are responsible for the UVA-dependent ROS formation, and that these browning products may be similar to the advanced glycation endproducts produced by ascorbylation of lens proteins under oxidative conditions. This work also presents an initial report of a chromatographic method to separate the UVA-sensitizers present in each of these protein preparations without the use of acid or base hydrolysis.

Topics: Animals; Ascorbic Acid; Cataract; Cattle; Crystallins; Glycosylation; Humans; In Vitro Techniques; Radiation-Sensitizing Agents; Solubility; Superoxides; Ultraviolet Rays

To give the levels of antioxidant nutrients in relation to age-related macular degeneration (AMD).. Pathologies Oculaires Liees a l'Age is a population-based study on cataract and AMD and their risk factors, carried out on 2584 inhabitants of Sete, France. Age-related macular degeneration was defined by findings from fundus photographs according to an international classification. Biological measurements were taken from fasting blood samples.. After multivariate adjustment, plasma alpha-to-copherol levels showed a weak negative association with late AMD (P = .07). Lipid-standardized plasma alpha-tocopherol levels showed a significant negative association with late AMD (P= .003): the risk of late AMD was reduced by 82% in the highest quintile compared with the lowest. Similarly, lipid-standardized plasma alpha-tocopherol levels were inversely associated with early signs of AMD (odds ratio, 0.72 [95% confidence interval, 0.53-0.98]; P=.04). No associations were found with plasma retinol and ascorbic acid levels or with red blood cell glutathione values.. These results suggest that vitamin E may provide protection against AMD. Only randomized interventional studies could prove the protective effect of vitamin E on AMD.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Cataract; Female; France; Humans; Macular Degeneration; Male; Middle Aged; Nutritional Status; Prevalence; Vitamin A; Vitamin E

The purpose of this study was to examine the correlates of self-reported cataract among older Americans, and specifically, to determine whether serum ascorbic acid levels are associated with a decreased prevalence of cataract. A national probability survey of Americans, the Second National Health and Nutrition Examination Survey (NHANES II), was conducted between 1976 and 1980. A total of 4001 participants were included between the ages of 60 and 74 years with data on serum ascorbic acid level and other variables of interest. A total of 252 women (12%) and 164 men (9%) reported a history of cataract. Serum ascorbic acid level was inversely associated with prevalence of cataract in multiple logistic regression analyses; each 1 mg/dl increase was independently associated with a 26% decrease in cataract (P = 0.03). Other independent correlates of cataract included increasing age, female sex, smoking, and diabetes mellitus (all P<0.01). We identified four correlates of cataract among older Americans: serum ascorbic acid level, increasing age, smoking, and diabetes mellitus. Ascorbic acid, a water-soluble antioxidant found in high concentrations in the lens, may be of importance for the prevention of cataract among older Americans.

Topics: Aged; Antioxidants; Ascorbic Acid; Cataract; Female; Humans; Male; Middle Aged; Nutrition Surveys; Prevalence; Retrospective Studies; Risk Factors; Self Disclosure; United States

To study oral administration of vitamin C on human aqueous humour ascorbate concentration.. High performance liquid chromatography (HPLC) coupled with electrochemical detector (ECD) was used. The effect of oral administration of various doses of ascorbic acid, 0 (control), 1.0, 1.5, 2.0, 3.0, and 5.0 g, on its concentration in aqueous humour, obtained from volunteer cataract patients was studied.. The concentration of ascorbic acid in aqueous humour of control group (without administration of vitamin-C tablet or drug containing ascorbic acid was (254 +/- 119) mg.L-1. This study revealed that the administration of 2.0 g of ascorbic acid saturate the aqueous humour and further increase in the dose (3.0 g and 5.0 g) did not increase its concentration in aqueous humour, although its concentration was increased in plasma.. Oral administration of 2.0 g of Vc is sufficient to saturate the aqueous humour where it may be helpful in controlling the intra-ocular pressure.

Topics: Aged; Aged, 80 and over; Aqueous Humor; Ascorbic Acid; Cataract; Female; Humans; Male; Middle Aged

Topics: Aged; Ascorbic Acid; Cataract; Contraindications; Female; Humans; Middle Aged

Cataract formation is believed to result from an oxidative insult which decreases the antioxidant defense of the lens, particularly the vitamin C concentration. Upon oxidation, vitamin C contributes with glucose to protein glycation. It also favours tryptophan oxidation, resulting in fluorescent peptide cross-links and protein insolubilisation. The relationship between cataract and lenticular vitamin C was analysed in 48 cataractous lens nuclei classified into four severity grades, considering the sum of the colour and opacity. Ascorbic and dehydroascorbic acids were quantified by HPLC-fluorescence. The Amadori product was measured by means of furosine, advanced glycation end products by their fluorescence and tryptophan concentration by HPLC-UV. The lens vitamin C concentration significantly decreased with cataract severity, but mostly in severe brown cataracts (around 88 mumol/100 g lens in mild cataracts, and 50 mumol/100 g in dark brown lenses). The dehydroascorbic acid concentration was always low and stable (1.9 +/- 0.9 mumol/100 g), as was the furosine concentration (0.4 +/- 0.1 mumol/g). The fluorescence of insoluble advanced glycated end products was significantly higher in severe cataracts than in milder ones. The peptide tryptophan content was stable but the tryptophan to tyrosine ratio decreased and was highly correlated to the ascorbic acid concentration. Vitamin C content appears to be a good indicator of cataract severity, suggesting that oxidation could take part in cataract progression.

Topics: Ascorbic Acid; Cataract; Disease Progression; Female; Fructose; Humans; Lens Nucleus, Crystalline; Lysine; Male; Sensitivity and Specificity; Tryptophan

HPLC/electrochemical detection was used to identify five major low MW water soluble electrochemically active molecules from the aqueous humor of three species of mammals: New Zealand White rabbits and humans (diurnal) and Sprague-Dawley rats (nocturnal). These molecules are L-cysteine (CYS), L-ascorbic acid (AA), glutathione (GSH), uric acid (UA) and L-tyrosine (TYR); all of these molecules have known antioxidant properties. Nocturnal rat aqueous humor is concentrated in two thiols: GSH (125 microM; n = 24 pooled eyes) and CYS (63 microM), in contradistinction to diurnal species which have high concentrations of AA. No deterioration of any of these antioxidants occurs in a synthetic aqueous humor mixture irradiated with a physiologically relevant spectral UV B dose of 30 mJ/cm2/h (5.5 UV equivalent sunlight hours). The same result occurred with addition of the endogenous aqueous humor UV B photosensitizer L-tryptophan. In a second set of experiments, human synthetic aqueous humor was subjected to hydrogen peroxide induced oxidant stress. The decay of antioxidants was CYS > GSH > AA > UA > TYR. The second highest concentrated antioxidant in human aqueous humor is TYR. Yet TYR failed to protect AA against H2O2-induced free radical damage in a synthetic aqueous humor model system (P = 0.10; ANOVA). The existence of multiple electrochemically active constituents and their thermodynamic interactions must be recognized when choosing animal models to evaluate human aqueous humor antioxidant defense.

Topics: Aged; Analysis of Variance; Animals; Antioxidants; Aqueous Humor; Ascorbic Acid; Cataract; Chromatography, High Pressure Liquid; Cysteine; Disease Models, Animal; Female; Glutathione; Humans; Hydrogen Peroxide; Mammals; Oxidants; Rabbits; Rats; Rats, Sprague-Dawley; Tryptophan; Tyrosine; Ultraviolet Rays; Uric Acid

Ideas prevailing in 1991 on hydrogen peroxide in the aqueous humor are outlined. They are critically examined under the light of our finding that the method used to establish aqueous humor levels of peroxide generates itself peroxide during the short time span of the analysis. This is due to the fact that the probe used, dichlorophenol indophenol (DCPIP), spontaneously auto-oxidizes in the presence of oxygen. It was concluded then that the level of hydrogen peroxide in the aqueous humor cannot be higher than about 0.3 microM, the detection limit of the DCPIP method. It was also concluded that the statement commonly made in the literature that aqueous humor hydrogen peroxide derives from the oxidation of ascorbate, an abundant component of that fluid, is based solely on the use of the DCPIP method, and so could easily be due to a methodological artifact. The same applies to the statement that the levels of hydrogen peroxide are very high in human senile cataracts. The surprising resistance to accept the results and conclusions of our 1992 publication is documented. Finally, the content is discussed of an oral presentation made at the 1997 ARVO Annual Meeting in which an important portion of our results and conclusions was confirmed, perhaps signaling a shift towards a wider acceptance of our findings.

Topics: 2,6-Dichloroindophenol; Animals; Aqueous Humor; Ascorbic Acid; Cataract; Cats; Cattle; Chickens; Chromatography, High Pressure Liquid; Dogs; Electrochemistry; Guinea Pigs; Humans; Hydrogen Peroxide; Indicators and Reagents; Papio; Rabbits; Ranidae; Rats; Research; Sheep

The Food and Drug Administration (FDA) is issuing an interim final rule to prohibit the use on foods of a claim relating to the relationship between antioxidant vitamins C and E and the risk in adults of atherosclerosis, coronary heart disease, certain cancers, and cataracts. This rule is in response to a notification of a health claim submitted under section 303 of the FDA Modernization Act of 1997 (FDAMA). FDA has reviewed statements that the petitioner submitted in that notification, and, in conformity with the requirements of FDAMA, the agency is prohibiting the claim because the statements submitted as the basis of the claim are not "authoritative statements" of a scientific body, as required by FDAMA; therefore, section 303 of FDAMA does not authorize use of this claim. As provided for in section 301 of FDAMA, this rule is effective immediately upon publication.

Topics: Adult; Arteriosclerosis; Ascorbic Acid; Cataract; Coronary Disease; Drug Approval; Food Labeling; Humans; Neoplasms; Risk Factors; United States; United States Food and Drug Administration; Vitamin E

Considerable evidence indicates that the maintenance of protein redox status is of fundamental importance for cell function, whereas structural changes in proteins are considered to be among the molecular mechanisms leading to diabetic complications. In this study, protein redox status and antioxidant activity were investigated in the lens and vitreous of diabetic and nondiabetic subjects. A significantly lower content of sulphydryl proteins was found in lens and vitreous of diabetic patients than in those of non-diabetic and control subjects. Moreover, an increased formation of protein-bound free sulphydryls and carbonyl proteins, indices of oxidative damage to proteins, was noted in diabetic patients. All these parameters were shown to be altered particularly when diabetes was complicated with retinal alterations. In addition, glutathione peroxidase activity and ascorbic acid levels, known to exert important antioxidant functions in the eye compartment, were found to be significantly decreased in the lens of diabetic patients, especially in the presence of retinal damage. This study indicates an alteration of protein redox status in subjects affected by diabetes mellitus; lens and vitreous proteins were found to be oxidized to a greater extent in the presence of retinal disease, together with a marked decrease of eye antioxidant systems. These results suggest that oxidative events are involved in the onset of diabetic eye complications, in which the decrease in free radical scavengers was shown to be associated with the oxidation of vitreous and lens proteins. Protein oxidation may, therefore, represent an important mechanism in the onset of eye complications in diabetic patients.

Topics: Aged; Antioxidants; Ascorbic Acid; Cataract; Cysteine; Diabetic Retinopathy; Eye; Female; Free Radical Scavengers; Glutathione Peroxidase; Humans; Lens, Crystalline; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Retina; Sulfhydryl Compounds; Vitreous Body

An inexpensive microplate assay method was developed to determine ascorbic acid in human aqueous humor samples. The method is based on the selective oxidation of ascorbic acid at alkaline pH and determination of ascorbic acid and other reducing substances in samples with bicinchoninic acid/CuSO4 before and after the alkaline treatment. The two-point measurement eliminates the effect of interfering substances, such as glucose, uric acid and glutathione, which are stable at alkaline pH. The advantages of the method are that it requires small sample volumes and allows handling of a large number of samples simultaneously.

Topics: Aqueous Humor; Ascorbic Acid; Cataract; Copper Sulfate; Humans; Quinolines; Trabeculectomy

Patients operated on for cataract (32 men/75 women, aged 50-93 years) were studied with respect to antioxidative agents in aqueous humor and serum. Extracellular glutathione peroxidase (eGSHPx) was demonstrated in aqueous humor for the first time by a radioimmunoassay, the concentration of eGSHPx being 0.66(0.18) mg/l (mean(S.D.)). The concentration of eGSHPx in serum was 3.81(0.84) mg/l, and its level in aqueous humor was 18(7)% of that level. Serum selenium had positive correlations with both serum eGSHPx (r = 0.34, P < 0.001) and aqueous humor eGSHPx (r = 0.25, P = 0.011). However, there was no relation between the concentrations of eGSHPx in aqueous humor and in serum, suggesting that the maintenance of eGSHPx levels in the two fluids is controlled by different mechanisms beside selenium status. There was an inverse correlation between age and serum eGSHPx but not with aqueous humor eGSHPx. The concentration of ascorbic acid in aqueous humor was 2.04(0.58) mmol/l, and it was closely correlated to the level of ascorbic acid in serum (0.052(0.032) mmol/l), r = 0.58 (P < 0.001). The ratio between the level of ascorbic acid in aqueous humor and that in serum was 39(17). There was no significant difference among patients with nuclear (n = 39), cortical (n = 20), posterior-subcapsular (n = 23) or mixed (n = 23) lens opacity with respect to levels of eGSHPx and ascorbic acid in serum and aqueous humor. Since serum ascorbic acid is related to ascorbic acid intake, its association to aqueous humor ascorbic acid indicates that dietary habits are important for maintaining that level which could play an important role in protecting ocular tissue against oxidative damage. The role of eGSHPx secreted into aqueous humor in the oxidant defence system needs further study.

Topics: Aged; Aged, 80 and over; Aqueous Humor; Ascorbic Acid; Cataract; Cataract Extraction; Creatinine; Female; Glutathione Peroxidase; Humans; Male; Middle Aged; Selenium; Serum Albumin

Mouse lens cultures were employed to study the progression of cataracts initiated by injection of buthionine sulfoximine, an inhibitor of glutathione (GSH) biosynthesis. Culture of lenses removed from untreated mice on postnatal day 7, for 48 hr in the presence of 4 mm BSO, resulted in only limited cataractous changes. To enable substantial progression of cataracts in vitro, it was therefore necessary to pretreat the mice with BSO prior to lens culture. A single injection of BSO (4 nmol mg-1 lens), administered on day 7, resulted in >90% depletion of lens GSH within 3 days, but no visible cataractous changes. The clear lenses were incubated for 29+/-1 hr at 37 degrees C in Medium HL-1, supplemented with EGF, insulin and Ca2+, in the presence or absence of BSO, and were scored for cataract development by previously described criteria. In the absence of BSO, only 4 of 10 lenses developed large opacities. However, in the presence of 4 mm BSO, 40 out of 45 experimental lenses developed opacities affecting at least 50% of the lens visual field and were scored as stages 1C-4, depending upon the extent and density of the cataracts. In addition, three lenses had opacities involving 20-50% of the field (stage 1B). By contrast, less than 10% of lenses from untreated mice incubated in the absence of BSO developed opacities. The cataracts developed in 4 mm BSO were accompanied by reduction of lens glutathione levels to <0.010 nmol mg-1 lens. They were almost completely prevented by 1 mm ascorbate, 2 mm GSH, 2 mm GSH monoethyl ester and 2 mm cysteamine. GSH and GSH ester maintained lens glutathione content between 0.1 and 0.2 nmol mg-1 in the presence of BSO, whereas ascorbate did not prevent near-total GSH depletion. The prevention of cataracts by thiols and ascorbate was confirmed by lens Na/K ratios not significantly different from those in control lenses. The above combination of GSH depletion in vivo by a single injection of BSO, followed 3 days later with lens culture in the presence of BSO, may yield a useful system to elucidate and control the biochemical mechanisms involved in oxidative cataract induction by this GSH-depleting agent.

Topics: Animals; Ascorbic Acid; Buthionine Sulfoximine; Cataract; Cysteamine; Glutathione; In Vitro Techniques; Lens, Crystalline; Mice; Potassium; Sodium; Sulfhydryl Compounds

The effect of several antioxidants and cysteine-elevating precursor drugs (prodrugs) was tested on lens damage occurring after in vitro exposure to low levels of 60Co-gamma-irradiation, to simulate in vitro the exposure to radiation in vivo of (1) astronauts (2) jet crews (3) military radiation accident personnel. Tocopherol (100 microM), ascorbic acid (1 mM), R-alpha-lipoic acid (1 mM), and taurine (0.5 mM) protected against radiation-associated protein leakage. MTCA and ribocysteine protected lenses against opacification, LDH and protein leakage, indicating that antioxidants and prodrugs of cysteine appear to offer protection against lens damage caused by low level radiation.

Topics: Animals; Antioxidants; Ascorbic Acid; Carbolines; Cataract; Cysteine; Dose-Response Relationship, Radiation; In Vitro Techniques; L-Lactate Dehydrogenase; Lens, Crystalline; Occupational Diseases; Radiation-Protective Agents; Rats; Ribose; Taurine; Thioctic Acid; Vitamin E

Topics: Age Factors; Ascorbic Acid; Cataract; Diet; Humans

We designed the present study to examine the cross-sectional relation between age-related lens opacities and vitamin C supplement use over a 10-12-y period before assessment of lens status in women without diagnosed cataract or diabetes. This design avoids biased measurement of nutrient intake that results when knowledge of lens opacities influences nutrition-related behavior or its reporting. The participants were 247 Boston-area women aged 56-71 y selected from the Nurses' Health Study cohort with oversampling of women with high or low vitamin C intakes. Lens opacities were graded with the Lens Opacification Classification System II. Use of vitamin C supplements for > or = 10 y (n = 26) was associated with a 77% lower prevalence of early lens opacities (odds ratio: 0.23; 95% CI: 0.09, 0.60) at any lens site and a 83% lower prevalence of moderate lens opacities (odds ratio: 0.17; 95% CI: 0.03, 0.85) at any lens site compared with women who did not use vitamin C supplements (n = 141) after adjustment for age and other potentially confounding variables. Women who consumed vitamin C supplements for < 10 y showed no evidence of a reduced prevalence of early opacities. These data, together with data from earlier experimental and epidemiologic studies, suggest that long-term consumption of vitamin C supplements may substantially reduce the development of age-related lens opacities.

Topics: Adult; Aged; Ascorbic Acid; Cataract; Cohort Studies; Confidence Intervals; Cross-Sectional Studies; Female; Humans; Middle Aged; Odds Ratio; Prevalence; Surveys and Questionnaires; Time Factors

Fifty male albino rabbits were studied. Ten animals served as controls. Forty animals were prepared to receive photorefractive keratectomy (PRK), including anesthesia, scraping of the corneal epithelial cells, etc. Twenty of these animals then received PRK with energy delivered by excimer laser (pulse rate = 20 Hz, fluence 250 mJ/cm2; number of pulses = 6032; cumulative UV dose = 1508J/cm2). The other 20 animals were exposed to the same operating microscope light as the PRK-treated animals, but they did not receive PRK. All three groups were divided into halves: the first half was immediately analyzed at 0 time, and the second half was observed 1 year later. Samples of aqueous humor and lens were analyzed. The levels of reduced and oxidized glutathione, hydrogen peroxide, ascorbic acid, and malondialdehyde were determined. Excimer laser-induced ultrastructural modifications of the lens, verified through scanning electron microscopy, were studied at the same intervals. Immediately after PRK, the biochemical parameters studied, both in aqueous humor and in lens of treated animals, showed significant differences. One year later, the observed biochemical variations in lens were still present, whereas aqueous humor values did not significantly differ from control values. Ultrastructural abnormalities of the lens appeared only 1 year after PRK In the animals that received only the preparation for PRK the biochemical and ultrastructural differences did not significantly vary as compared to the data obtained from control animals. These findings suggest that the biochemical and ultrastructural lens alterations induced by PRK may represent events relevant to cataractogenesis in the rabbit.

Topics: Animals; Aqueous Humor; Ascorbic Acid; Cataract; Cornea; Glutathione; Hydrogen Peroxide; Lasers, Excimer; Lens, Crystalline; Male; Malondialdehyde; Microscopy, Electron, Scanning; Photorefractive Keratectomy; Rabbits; Radiation Injuries, Experimental

This study revealed a marked stereospecificity in the prevention of buthionine sulfoximine-induced cataract, and in the protection of lens antioxidants, in newborn rats by alpha-lipoate, R- and racemic alpha-lipoate decreased cataract formation from 100% (buthionine sulfoximine only) to 55% (buthionine sulfoximine + R-alpha-lipoic acid) and 40% (buthionine sulfoximine + rac-alpha-lipoic acid) (p<0.05 compared to buthionine sulfoximine only). S-alpha-lipoic acid had no effect on cataract formation induced by buthionine sulfoximine. The lens antioxidants glutathione, ascorbate, and vitamin E were depleted to 45, 62, and 23% of control levels, respectively, by buthionine sulfoximine treatment, but were maintained at 84-97% of control levels when R-alpha-lipoic acid or rac-alpha-lipoic acid were administered with buthionine sulfoximine; S-alpha-lipoic acid administration had no protective effect on lens antioxidants. When enantiomers of alpha-lipoic acid were administered to animals, R-alpha-lipoic acid was taken up by lens and reached concentrations 2- to 7-fold greater than those of S-alpha-lipoic acid, with rac-alpha-lipoic acid reaching levels midway between the R-isomer and racemic form. Reduced lipoic acid, dihydrolipoic acid, reached the highest levels in lens of the rac-alpha-lipoic acid-treated animals and the lowest levels in S-alpha-lipoic acid-treated animals. These results indicate that the protective effects of alpha-lipoic acid against buthionine sulfoximine-induced cataract are probably due to its protective effects on lens antioxidants, and that the stereospecificity exhibited is due to selective uptake and reduction of R-alpha-lipoic acid by lens cells.

Topics: Animals; Animals, Newborn; Ascorbic Acid; Buthionine Sulfoximine; Cataract; Female; Glutathione; Glutathione Disulfide; Lens, Crystalline; Methionine Sulfoximine; Pregnancy; Rats; Rats, Sprague-Dawley; Stereoisomerism; Thioctic Acid; Vitamin E

Twenty male albino rabbits were studied. Four animals served as controls; the remaining 16 animals represented the treated group. All the treated animals were exposed to the same amount of energy delivered by the excimer laser (pulse rate: 20 Hz, fluence 250mJ/cm2; number of pulses: 6032; cumulative UV dose 1508 J/cm2) and were divided into eight groups of 2 animals each (four eyes). Samples of aqueous humor and lens were obtained at the following intervals: 5, 10, 20 and 40 min and 1, 2, 3 and 4 weeks after photorefractive keratectomy (PRK). The levels of reduced and oxidized glutathione, hydrogen peroxide, ascorbic acid and malondialdehyde were determined. Aqueous humor analyses, twenty min after PRK, showed no significant differences with pre-treatment values, while the observed variations in lens were constantly present over the entire follow-up period (one month). These findings suggest that the biochemical lens alterations induced by PRK may represent the earliest events relevant to cataractogenesis in the rabbit.

Topics: Animals; Aqueous Humor; Ascorbic Acid; Cataract; Cornea; Glutathione; Glutathione Disulfide; Hydrogen Peroxide; Lasers, Excimer; Lens, Crystalline; Male; Malondialdehyde; Oxidative Stress; Photobiology; Photorefractive Keratectomy; Rabbits; Time Factors

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Cardiovascular Diseases; Cataract; Copper; Diabetes Mellitus; Diet; Humans; Lens, Crystalline; Middle Aged; Oxidation-Reduction; Peptides; Reference Values; Regression Analysis; Tryptophan

In contrast to conventional view that glucose is the sole glycating agent, ascorbate has now emerged as a potential precursor of advanced glycation products in lenses during cataractogenesis, owing to the high concentration present in human lens. The effects of high hexose environment in vitro and in vivo on the disruption of redox equilibrium of ascorbate (ASA) to dehydroascorbate (DHA), which is required for ascorbate-mediated crystallin modification by the Maillard reaction during cataractogenesis were examined. Organ culture experiments were performed with rat lenses that were first exposed to high galactose levels in vitro and in vivo and then incubated with 1-14C-labeled ASA, DHA or DKG (2,3-diketogulonic acid). Formation of ASA degradation products as a function of time was assessed by radiometric TLC method. Upon incubation with ASA or DHA, an elevated level of the degradation product, DKG, was detected in lenses exposed to galactose in vivo and in vitro. ASA uptake was significantly enhanced in the galactosemic lenses as compared to controls (P = 0.01). Regeneration of ASA from DHA in both galactose treated and galactosemic lenses was impaired when compared to control lens which completely converted DHA from the medium into ASA. Surprisingly, the galactose exposed lenses showed enhanced permeability to DKG which was picked up readily from the medium in contrast to normal healthy lenses which remained impermeable to DKG. Galactose exposed lenses both in vitro and in vivo showed a 5-9-fold increase in crystallin bound Schiff base-linked radioactivity when incubated with 1-14C-labeled ASA or DHA. As a preamble to the question of whether lens pigmentation predisposes towards ascorbate oxidation, lens homogenate from normal young and old pigmented cataractous lenses were incubated with [1-14C]ASA. After 2 days, ASA levels were found to have decreased by 74% and DKG levels increased by 48% in brunescent lens as compared to the young lens. These data demonstrated that profound abnormalities in ASA metabolism exist in lenses exposed to a high sugar environment suggestive of a breakdown of the redox equilibrium of ASA to DHA and a loss of membrane permeability barrier for DKG. The latter would further contribute toward a ASA-catalysed Maillard reaction in the redox impaired lens.

Topics: 2,3-Diketogulonic Acid; Animals; Ascorbic Acid; Cataract; Crystallins; Dehydroascorbic Acid; Galactose; Humans; Lens, Crystalline; Male; Organ Culture Techniques; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Time Factors

The Emory mouse is the best model for age-related cataract. In this work we compare the effects of feeding a control diet (C) with a diet restricted (R) by 40% relative to C animals. In the R animals, median lifespan was extended by 40%. The proportion of R mice with advanced cataract was lower than C mice as early as 5 months of age. The mean grade of cataract was lower in R animals, beginning at 11 months and continuing until the end of the study. Ascorbate levels in R plasma and liver were 41-56% of C animals. There was no difference between diet groups with respect to lens ascorbate. Aging was associated with a decrease in ascorbate in lenses and kidneys in C and R mice. By 22 months, R animals had 48% higher liver glutathione levels than C mice. Liver glutathione levels were maximal at 12 months. Plasma glucose levels were > 27% lower in R animals at 6.5 and 22 months, and there was a 14% increase in glucose levels upon aging for both diet groups. In R mice, glycohemoglobin levels were 51% lower and tail collagen breaktime was decreased by 40%, even in younger animals. Collagen breaktime increased > 360% upon aging for both diet groups. Rates of production of urinary oxo8dG and oxo8G were higher in R animals compared with C animals, and increased upon aging. C animals exhibited more cancer and dermatological lesions, but less tail tip necrosis and inflamed genitals than R mice. These data allow evaluation of several theories of aging.

Topics: Animals; Ascorbic Acid; Cataract; Collagen; DNA; Energy Intake; Glucose; Glutathione; Glycated Hemoglobin; Longevity; Mice; Mice, Inbred Strains; Oxidation-Reduction; Prevalence; RNA; Skin; Tail

The in vitro effect of glucose on cultured rat lenses was correlated with (i) the time-dependent leakage of lactate dehydrogenase (LDH) into defined medium; (ii) the appearance of the lens under the dissection microscope; and (iii) the leakage of lens cytosolic proteins. A protective effect of 1 mM Vitamin C (VC) was also found: the extent of opacification, LDH and gamma-crystallin release were reduced if 1 mM VC was included in the medium. Using the above parameters provides a new and more rapid technique to follow lens opacification in vitro.

Topics: Animals; Ascorbic Acid; Cataract; Cell Death; Cells, Cultured; Crystallins; Electrophoresis, Polyacrylamide Gel; Female; Glucose; L-Lactate Dehydrogenase; Lens, Crystalline; Rats; Rats, Wistar

Dietary restriction can effectively extend lifespan and retard many age-related debilities. One hypothesis to explain the beneficial effects of dietary restriction is that it prolongs maintenance of cellular homeostasis by limiting endogenous oxidative stress and preserves oxidative defense mechanisms during aging. Ascorbate, a primary antioxidant, may play a major role in preventing oxidative damage. Ascorbate levels were determined in dietary restricted (R) and control (C) Emory mice, a strain which develops age-related cataract due in part to oxidative damage to lens proteins. Mice which consumed a diet restricted by 40% in calories had lower ascorbate concentrations in plasma, liver and kidney. Nevertheless, R animals showed significantly delayed progression of cataract which extended over the entire second half of life. The R diet did not result in different ascorbate levels in this lens. Aging was associated with a decrease in ascorbate in all the examined tissues except lens of both the R and C groups. It is not clear from these data that ascorbate is a prominent factor in the delay of cataract formation or other debilities in R Emory mice. However, it also appears unlikely that lens ascorbate is cataractogenic.

Topics: Aging; Animals; Ascorbic Acid; Cataract; Diet; Lens, Crystalline; Mice

Transferrin and Fe concentrations increase in the intraocular fluids in pathological conditions and the lens accumulates Fe during ocular inflammation. Tissues take up Fe from transferrin by two mechanisms, receptor-medicated endocytosis of diferric transferrin and a process occurring at the cell membrane which may be mediated by an oxido-reductase. However, Fe metabolism, transport and storage have not been previously investigated in the lens. This study was designed to characterize the uptake of Fe from transferrin by lens epithelial cells in culture.. Primary, secondary and tertiary cultures of canine lens epithelial cells and cultures obtained from cataractous lenses were studied. Uptake of 59Fe from transferrin by these cultured cells was measured. Transferrin receptor populations were determined in receptor-binding assays.. There was a distinct relationship between the amount of Fe-transferrin added and the amount of Fe taken up, which was linear for the primary cultures but significantly reduced for the secondary, tertiary and cataract cultures (252 +/- 21, 169 +/- 14, 153 +/- 14 and 96 +/- 2 ng Fe/mg protein, respectively). Transferring receptor expression in lens cell cultures was reduced 10-fold within 2 days of addition of serum to cells grown in low-Fe, serum-free medium for 1 week.. The reduction of Fe uptake by the subcultured and cataract cell lines probably reflects a decrease in transferrin receptor expression and in the activity of an alternative pathway for Fe transferrin uptake occurring over time. This reduced Fe uptake may result from long-term exposure to relatively high Fe concentration in the media. A reduction in the expression of the transferrin receptor after incubation with high concentrations of Fe supports this conclusion.

Topics: 2,2'-Dipyridyl; Animals; Ascorbic Acid; Biological Transport; Cataract; Cells, Cultured; Dogs; Epithelium; Iron; Iron Radioisotopes; Lens, Crystalline; Receptors, Transferrin; Transferrin

Estimation of cadmium and vitamin C was performed in the blood and lens of smokers in three age groups up to a maximum age of 58, habituated to smoking a minimum of 10 beedies a day for many years, as well as those of non-smokers in the same age groups. Only nuclear cataracts with or without posterior or anterior subcapsular cataract were chosen. It was found that there was a significant accumulation of cadmium in both the blood and the lens of the smokers. Such an accumulation of cadmium might have a role in cataractogenesis in chronic smokers. In a similar experiment, with smokers and non-smokers of two age groups up to a maximum age of 40, both without cataract, increased levels of cadmium were found in the blood of smokers only, though the extent of accumulation was not as high as in chronic smokers of higher age groups. Vitamin C content of lens was on the lower side of normal in both chronic smokers of beedies in the two age groups and non-smokers with nuclear cataract with or without posterior and anterior subcapsular cataract, and there was no significant change brought about by smoking. Vitamin C levels in blood were towards the lower side of the normal in smokers and non-smokers with and without cataract.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Cadmium; Cataract; Cataract Extraction; Double-Blind Method; Humans; Lens, Crystalline; Male; Middle Aged; Risk Factors; Smoking

The effect of cytochalasin D (CD), an actin monomer-stabilizer, has been studied on cataract development in rat lenses. Cataractogenesis was induced by incubating the rat lenses in medium 199 (M199) containing 10(-5) M CD; by the end of 24 h, lenses first developed a visible opacity. The increased lactate dehydrogenase (LDH) activity in the culture medium, leakage of lens cytosolic proteins into the culture medium and observable development of opacity through a dissection microscope were correlated with cell damage associated with cataract formation. Non-denaturing polyacrylamide gel electrophoresis was used to separate three lens LDH isoenzymes. The effect of 1 mM vitamin C (VC) in reducing LDH leakage was also examined. The protective effect of VC on CD-initiated cataractous lenses is significant. This suggest that a portion of the opacity and lens damage may involve oxidative damage to the membrane-cytoskeleton complex which is started by CD, but partially prevented by VC

Topics: Animals; Ascorbic Acid; Cataract; Culture Media; Cytochalasin D; Electrophoresis, Polyacrylamide Gel; Female; Isoenzymes; L-Lactate Dehydrogenase; Lens, Crystalline; Nitroblue Tetrazolium; Organ Culture Techniques; Rats; Rats, Wistar

In developing chick embryos, hydrocortisone induces cataract formation following a decrease in lens glutathione content but an increase in lipid peroxide content in lens, blood and liver. The preventive effects of ascorbic acid 2-O-alpha-glucoside (AA-2G) on these parameters were compared on cataract formation with those of ascorbic acid (AsA) and ascorbic acid 2-O-phosphate (AA-2P). In these tissues, AA-2G inhibited a decrease in glutathione content and an increase in lipid peroxide content more effectively than either AsA or AA-2P. Various tissues including lens and liver have alpha-glucosidase activity, strongly suggesting that AsA is enzymatically liberated from AA-2G in these tissues. In summary, these results suggest that AA-2G exerts a potent anti-cataract activity via a reduction in oxidative damage through AsA release.

Topics: alpha-Glucosidases; Animals; Ascorbic Acid; Cataract; Chick Embryo; Glutathione; Hydrocortisone; Lens, Crystalline; Lipid Peroxides; Liver

Topics: Animals; Aqueous Humor; Ascorbic Acid; beta Carotene; Carotenoids; Cataract; Crystallins; Diabetes Mellitus, Experimental; Disease Models, Animal; Drug Combinations; Female; Image Processing, Computer-Assisted; Rats; Rats, Wistar; Vitamin E; Vitamins; Vitreous Body

It was evaluated whether ArF 193 nm excimer laser corneal surgery represents a risk factor in cataractogenesis. For this purpose, 20 male albino rabbits underwent a photorefractive keratectomy and biochemical analyses on aqueous humour (hydrogen peroxide, ascorbic acid, and reduced and oxidized glutathione) and on lens (malondialdehyde, reduced and oxidized glutathione) were performed. In the aqueous humour of all treated animals a significant increase in hydrogen peroxide and in oxidized glutathione and a concomitant decrease in ascorbic acid and reduced glutathione concentration were observed. Moreover, all these variations were significantly correlated with the cumulative UV dose used. In the lens, after excimer laser corneal surgery, there was a dramatic loss of reduced glutathione and a parallel increase in oxidized glutathione levels. Malondialdehyde concentration was also increased, but only at the highest UV exposure. Moreover, all these variations were significantly correlated with the cumulative UV dose used. These findings demonstrate that the exposure of aqueous humour and lens to the secondary radiation generated after ArF 193 nm excimer laser corneal photoablative keratectomy induces biochemical modifications which are known to be markers of cataractogenesis.

Topics: Animals; Aqueous Humor; Ascorbic Acid; Cataract; Cornea; Glutathione; Hydrogen Peroxide; Laser Therapy; Lens, Crystalline; Male; Malondialdehyde; Oxidation-Reduction; Rabbits; Radiation Dosage; Refractive Surgical Procedures; Risk Factors; Ultraviolet Rays

A major and a minor ascorbate free radical (AFR) reductase were separated from the soluble fraction in the human lens cortex by DEAE-cellulose ion-exchange column chromatography. These AFR reductases also exhibited diaphorase activity using dichlorophenolindophenol and ferricyanide as electron acceptors. The major AFR reductase was partially purified by 5'AMP-Sepharose 4B affinity column chromatography. This partially purified AFR reductase showed a single band of diaphorase activity in native polyacrylamide disc gel electrophoresis. This activity band corresponded to the major protein observed in protein staining by Coomassie Brilliant Blue. However, the protein staining by Coomassie Brilliant Blue showed this activity band surrounded by diffused staining. Molecular weight of the partially purified AFR reductase was determined to be 32 kDa by gel filtration, and the apparent Km value for AFR was about 15 microM. This major lens AFR reductase could be distinguished from soluble Neurospora, Euglena and cucumber AFR reductases, and from two ubiquitous enzymes with reduction activity of AFR and/or foreign compounds, ie, NADH-cytochrome b5 reductase and DT-diaphorase, by their molecular weights, Km values and/or ion-exchange chromatographic behaviors.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Cataract; Chromatography, Affinity; Chromatography, Ion Exchange; Dihydrolipoamide Dehydrogenase; Electrophoresis, Polyacrylamide Gel; Free Radicals; Humans; Kinetics; Lens Cortex, Crystalline; Middle Aged; Molecular Weight; NADH, NADPH Oxidoreductases; Oxidoreductases; Solubility

It was reported previously that dietary ascorbate (ASC) delays the development of galactose-induced cataract in guinea pigs compared to the rate which is observed in ASC-deficient animals. Experiments were conducted to explore the possible mechanism of this phenomenon. Guinea pigs were fed for a period of up to 4 weeks either a normal diet (1 g ASC/kg diet) or a scorbutic diet (< 0.04 g ASC/kg diet) combined with 10% galactose in the drinking water. After 2 weeks, levels of ASC in animals on the scorbutic diet decreased by 95% in the aqueous humor and by 78% in the lens. Slit lamp examination showed that galactose-induced vacuoles in the lens equator formed at a significantly faster rate in the scorbutic animals. However, examination of biochemical parameters in whole lenses of the two groups of animals after 2 weeks showed no significant differences with regard to accumulation of galactose and galactitol, decreases in the levels of myoinositol, taurine and GSH or changes in cation concentrations. In order to examine possible regional changes in the lenses, various parameters were studied in the lens capsule-epithelium. On day 4, the capsule epithelia of scorbutic animals on a galactose diet had a content of galactitol two-and-a-half times higher than that of normal galactose-fed animals. Scorbutic conditions also intensified the loss of Na(+)-K+ ATPase activity in the lens capsule-epithelium caused by galactose feeding. Oxidized glutathione was not detectable in the lens capsule epithelia of any of the animals studied. Hexose monophosphate shunt activity was elevated in lenses of normal galactose-fed animals during the first hour of culture after death whereas lenses of scorbutic galactose-fed animals were not. Consistent with the in vivo findings, galactitol accumulation in dog lens epithelial cells exposed to 30 mM galactose was significantly inhibited by the presence of either ASC or dehydroascorbate (DHA) in the medium. Hexose monophosphate shunt activity in the cells was stimulated to two-and-a-half times its initial level by either 1 mM DHA or 30 mM galactose and slightly more than three-fold by a combination of the two challenges. The results suggest that decreased polyol accumulation in the lens epithelium of the normal galactose-fed guinea pig, which has a high level of ASC in the aqueous humor, accounts for the delay in onset of cataract compared to that for the ASC-deficient animal.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Aqueous Humor; Ascorbic Acid; Cataract; Cells, Cultured; Dehydroascorbic Acid; Dogs; Female; Galactitol; Galactose; Glutathione; Guinea Pigs; Hydrogen Peroxide; Inositol; Lens, Crystalline; NADP; Sodium-Potassium-Exchanging ATPase

The purpose of this study was to examine prospectively the association between reported use of vitamin supplements and risk of cataract and cataract extraction.. The study population consisted of 17,744 participants in the Physicians' Health Study, a randomized trial of aspirin therapy and beta-carotene among US male physicians 40 to 84 years of age in 1982 who did not report cataract at baseline and provided complete information about vitamin supplementation and other risk factors for cataract. Self-reports of cataract and cataract extraction were confirmed by medical record review.. During 60 months of follow-up, there were 370 incident cataracts and 109 cataract extractions. In comparison with physicians who did not use any supplements, those who took only multivitamins had a relative risk of cataract of 0.73 after adjustment for other risk factors. For cataract extraction, the corresponding relative risk was 0.79. Use of vitamin C and/or E supplements alone was not associated with a reduced risk of cataract, but the size of this subgroup was small.. These data suggest that men who took multivitamin supplements tended to experience a decreased risk of cataract and support the need for rigorous testing of this hypothesis in large-scale randomized trials in men and women.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Cataract; Double-Blind Method; Humans; Male; Middle Aged; Physicians; Prospective Studies; Risk Factors; United States; Vitamin E; Vitamins

Aqueous humor from children with retinoblastoma obtained at enucleation and from eyes with adult cataracts were assayed with electrochemical liquid chromatography (Model 5500 Coulochem electrode array system) for metabolites of tyrosine, tryptophan metabolic pathways, catecholamine degradation pathways and ascorbate. More than 20 metabolites were identified in human aqueous for the first time. High levels of ascorbate were found in aqueous of eyes with adult cataracts (254, 336 ng/ml). Tyrosine metabolism in both sets of eyes was through dopamine. Vandylmandelic acid (VMA), homovanillic acid (HVA), and 3-methoxy, 4-hydroxyphenylglycol (MHPG) were all detected in retinoblastoma eyes. Although eyes with either adult cataracts or childhood retinoblastoma convert tryptophan through the serotonin pathway, retinoblastoma eyes metabolize tryptophan through the kynurenine pathway to a greater degree than adult cataract eyes.

Topics: Adult; Amino Acids; Aqueous Humor; Ascorbic Acid; Cataract; Catecholamines; Child, Preschool; Chromatography, High Pressure Liquid; Eye Neoplasms; Humans; Retinoblastoma

The effect of dietary supplementation with acetylsalicylic acid on the increased modification, and susceptibility to modification, of lens crystallins from the streptozocin diabetic rat, has been determined. This was done by the measurement of characteristic markers of protein post-translational oxidative modification and glycation, in beta L crystallins purified from the lenses of control, diabetic and acetylsalicylic acid-supplemented diabetic animals, with no further manipulations, and again following the application of an in vitro graded oxidative insult. Crystallins prepared from the diabetic, in comparison with control animals, exhibited a higher level of bityrosine- and AGEP-like fluorescence as well as a loss of tryptophan fluorescence and sulphydryl groups. Exposure to an oxidative insult (in the form of CuSO4 and ascorbate) increased all parameters in beta L crystallins, irrespective of their source. However, the effects were most pronounced in the diabetic in which the effects of oxidative stress were always greater than the control crystallin. Dietary supplementation of the diabetic group with acetylsalicylic acid (100 mg kg-1 body weight day-1) had a marked effect in decreasing the level of modification induced in diabetic crystallins, by in vitro metal catalysed oxidative stress, lowering the levels of AGEP- and bityrosine-like fluorescence and carbonyl group formation. Increasing the oxidative stress by addition of increasing concentrations of H2O2, induced stress proportional increases in the indicators of protein modification in all beta L crystallins, irrespective of source. The increase in damage in relation to H2O2 concentration was greater in those crystallins from diabetic animals, revealing a greater susceptibility to such oxidative stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Ascorbic Acid; Aspirin; Cataract; Copper; Crystallins; Diabetes Mellitus, Experimental; Hydrogen Peroxide; Lens, Crystalline; Male; Oxidation-Reduction; Rats; Rats, Wistar

The aim was to test whether cataract is associated with higher lifetime exposure to sunlight, and whether antioxidants protect against cataract.. This was a cross sectional survey of eye disease, with assessment of antioxidant status in a subgroup.. Hong Kong fishing communities in 1989.. 685 men and women aged 55 to 74 years old were included in the study, of whom 367 (54%) attended hospital for detailed examination.. At a mobile clinic visual acuity and lens opacities were assessed, and using a questionnaire, occupational history and lifetime exposure to sunlight. At hospital ophthalmic measurements were repeated and blood was taken for measurement of plasma vitamin C, vitamin E, and total carotenoids, and red cell activities of glucose-6-phosphate dehydrogenase, glutathione peroxidase, superoxide dismutase, and catalase. Higher grades of cataract (particularly nuclear cataract) tended to be more common in subjects with the most sun exposure, although not to the point of statistical significance. In contrast to earlier studies, no association was found with antioxidant status.. The findings give some support to the hypothesis that sunlight causes cataract. The absence of a relation to antioxidant status may be because blood levels of antioxidants at one point in time do not adequately reflect a subject's past metabolic state, and particularly the past activity of antioxidants in the lens.

Topics: Aged; Ascorbic Acid; Carotenoids; Cataract; Female; Fisheries; Hong Kong; Humans; Male; Middle Aged; Oxidoreductases; Sunlight; Vitamin E

Acetone is one of the most commonly used industrial solvents. Recent literature indicated that in guinea pigs, but not rabbits, acetone is cataractogenic and that elevated acetone exposure is also associated with depressed aqueous ascorbate levels. Other work indicated that aqueous and lens levels of ascorbate are closely linked and that depressed ascorbate status is related to cataract. Taken together, these papers suggested that acetone exposure, depressed ascorbate levels, and cataract are related, possibly causally. While the possibility that acetone is cataractogenic presented a major health concern, it also presented an opportunity to develop a new model of cataract in which hypotheses regarding anticataractogenic effects of ascorbate could be tested. Albino hairless guinea pigs are immunocompetent animals derived from albino Hartley guinea pigs. Animals were fed diets containing low (4.9 mg/day) and high (55 mg/day) levels of ascorbate. This resulted in distinct groups of animals, one with high tissue ascorbate levels and the other with low, but nonscorbutic ascorbate levels. The tissue levels of ascorbate and the relationship between tissue ascorbate levels and dietary intake indicate that with respect to ascorbate uptake, transport, and concentration, these animals are identical to the standard albino Hartley animals. Daily exposure to acetone was extended for 6 months, with a total applied dose of 65 ml. Absorption of the solvent was maximized by the use of hairless animals. Despite exposure of the animals to higher levels of acetone, in no case (n = 20) were cataracts observed over a 2-year period. This is consistent with results using rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acetone; Administration, Topical; Animals; Ascorbic Acid; Biological Availability; Cataract; Diet; Guinea Pigs; Lens, Crystalline

The effect of ascorbic acid 2-O-alpha-glucoside (AA-2G) on hydrocortisone (HC)-induced lens opacity in developing chick embryo was examined and compared with those of ascorbic acid (AsA) and ascorbic acid 2-phosphate (AA-2P). The opacity was dose-dependently inhibited by a single administration of 10 or 20 mumol/egg of AA-2G and by three repeated administrations of 1, 3 or 10 mumol/egg of AA-2G. AA-2G was the most effective among the three compounds. Glucose did not enhance the preventive effect of AsA against HC-induced opacity, and neither dehydro ascorbic acid nor glucose also prevented HC-induced cataract. In the histological study, we observed many small vacuoles in the nuclear region of the opaque lens treated with HC. AA-2G inhibited the formation of such vacuoles, an effect closely correlated with the prevention of cataract formation.

Topics: Animals; Ascorbic Acid; Cataract; Chick Embryo; Dose-Response Relationship, Drug; Hydrocortisone; Lens, Crystalline; Vacuoles

We evaluated nutritional risk factors for cataract in 660 subjects enrolled in the Baltimore Longitudinal Study on Aging. As a part of a regular cycle of visits, nuclear and cortical lens photographs were taken over a 2-year period. Measurements of plasma antioxidants (beta-carotene, ascorbic acid, and alpha-tocopherol) were obtained in this cohort as part of the study protocol up to 4 years before lens photographs were taken. We found that plasma beta-carotene and ascorbic acid levels were not associated with risk of nuclear or cortical lens opacities. Higher levels of plasma alpha-tocopherol, however, were associated with a reduced risk of nuclear opacity [odds ratio (OR) for highest quartile vs lowest quartile = 0.52, 95% confidence interval (CI) = 0.27-0.98; OR for middle two quartiles vs lowest quartile = 0.55, 95% CI = 0.30-0.98], after adjusting for age, sex, and history of diabetes. Middle levels of alpha-tocopherol were associated with a reduced risk of cortical opacity (OR = 0.57, 95% CI = 0.32-1.02), but no such association was observed for high levels of alpha-tocopherol. We constructed an index of overall antioxidant status, which indicated that higher levels of plasma antioxidants were not associated with risk of nuclear or cortical opacities.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Carotenoids; Cataract; Diet; Female; Humans; Lens Cortex, Crystalline; Lens Nucleus, Crystalline; Male; Middle Aged; Prevalence; Risk Factors; Vitamin E

1-[(2s)-3-Mercapto-2-methylpropionyl]-L-proline (captopril), an antihypertensive and free radical scavenger, protected the rabbit lens from peroxidative and oxidative damage induced by 1 mM diquat in vitro. To evaluate the anticataract efficacy of captopril, an experimental group of five rabbits was treated with topical captopril (1% in 0.15 M NaCl, w/v), and 50 microliters was instilled onto both eyes four times a day for a total of 8 weeks. Following the same procedure, the eyes of five rabbits were treated with topical 0.15 M NaCl as a control for captopril treatment. At the end of the first week of treatment, a single intravitreal dose of 120 nmole diquat in 30 microliters of 0.15 M NaCl was injected into the right eye of each rabbit of both the groups. As a control for intravitreal diquat injection, the left eye of all the rabbits were injected with the diluent, 30 microliters per eye. The intravitreal diquat or its diluent injection was only for one time. From slit-lamp biomicroscopic observation of the diquat-injected right eyes, the anticataract effect of captopril in the treatment group was indicated by the finding that in four of five rabbits the cataract did not advance; whereas in four of five rabbits treated with the diluent the cataract progressed to grade 3. The lenses in the diluent-injected control left eyes of the rabbits treated with the captopril or diluent were normal. However, since the number of animals used for the in vivo studies was few, further confirmation of the anticataract effect of captopril is necessary. In diquat-injected right eyes of animals treated with captopril, the integrated rate of O2- production was about 50% less (p less than .001) in the aqueous humor, vitreous humor, and lens, compared with O2-, 33.49 +/- 2.26 microM (mean +/- SEM) in the aqueous humor, 17.12 +/- 0.75 microM in the vitreous humor, and 31.44 +/- 1.29 nmole/g wet weight in the lens of the diquat-injected right eyes treated with the diluent. Similar significant (p less than .01) differences in the production of .OH and H2O2 in eye tissues were also observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Administration, Topical; Animals; Antioxidants; Ascorbic Acid; Captopril; Cataract; Diquat; Eye; Female; Hydrogen Peroxide; Lens, Crystalline; Lipid Peroxidation; Male; Rabbits; Sulfhydryl Compounds; Superoxides

To examine prospectively the association between dietary intake of vitamins C and E, carotene, and riboflavin and cataract extraction in women.. Prospective cohort study beginning in 1980 with eight years of follow up.. 11 states of the United States.. Female registered nurses who were 45 to 67 years of age. 50,828 women were included in 1980 and others were added as they became 45 years of age.. Incidence of extraction of senile cataracts.. 493 cataracts were extracted during 470,302 person years of follow up. Intake of carotene and vitamin A was inversely associated with cataract: in multivariate analyses, women in the highest fifth of total vitamin A intake (excluding supplements) had a 39% lower risk of cataract relative to women in the lowest fifth (relative risk 0.61; 95% confidence interval 0.45 to 0.81). Neither riboflavin nor dietary vitamins E or C were associated with cataract in a multivariate analysis. Among specific food items spinach (rather than carrots, the greatest source of beta carotene) was most consistently associated with a lower relative risk. The risk of cataract was 45% lower among women who used vitamin C supplements for 10 or more years(relative risk 0.55 (0.32 to 0.96)), but no association was noted for multivitamin intake.. Dietary carotenoids, although not necessarily beta carotene, and long term vitamin C supplementation may decrease the risk of cataracts severe enough to require extraction.

Topics: Aged; Ascorbic Acid; Carotenoids; Cataract; Cataract Extraction; Diet; Female; Humans; Middle Aged; Prospective Studies; Riboflavin; United States; Vitamin A; Vitamin E; Vitamins

A blue fluorophore, named LM-1 was isolated from human eye lens crystallins. The fluorescence property of LM-1 (excitation/emission, 366/440 nm) is similar to the fluorescence originating during non-enzymatic glycation (Maillard reaction) of proteins with the reducing sugars. LM-1 accumulates linearly with age in highly cross-linked water insoluble crystallins and is present at higher levels in cataractous lenses. The fluorophore could be synthesized by incubation of bovine serum albumin (BSA) with ribose, but not with glucose or fructose. Incubation of bovine lens crystallins with ascorbic acid (ASA) and its oxidative products, dehydroascorbic acid (DHA) and 2,3-diketogulonic acid (DKG) in presence of oxygen resulted in LM-1 formation. When oxygen was removed from the system, only DHA and DKG could synthesize LM-1, but not ASA, suggesting that ASA oxidation is obligatory for LM-1 synthesis. Modification of lysine residues on BSA prior to incubation with ribose resulted in corresponding decrease in LM-1 formation. Since ASA concentration is unusually high in lens and has been found to be a powerful glycating agent of crystallins and since LM-1 does not form with hexoses, it is likely that ASA is the major precursor of LM-1.

Topics: Adult; Aged; Aging; Animals; Ascorbic Acid; Cataract; Cattle; Chromatography, High Pressure Liquid; Crystallins; Fluorescence; Humans; Lens, Crystalline; Maillard Reaction; Pronase; Ribose

Since many years experimental evidences have suggested an association between nutrition and lens opacities. A dietary deficiency of antioxidants and reactive oxygen scavengers may be involved in the pathogenesis of the "idiopathic" human senile cataract, as it has been demonstrated in some experimental cataracts. We tested the levels of ascorbic acid (vit. C), alpha-tocopherol (vit. E), reduced glutathione (GSH) and malondialdehyde (MDA) in the plasma or in the red blood cells (RBC) of 42 patients who were affected by surgically significant cataract and of 40 age-matched controls. Plasma vit. C mean level was 4.46 gamma/ml in cataracts and 4.62 gamma/ml in controls, while vit. E level was 7.70 and 7.09 gamma/ml respectively. RBC GSH was found to be 342 gamma/ml in cataracts and 346 in controls, while the MDA content was 4.06 picoMol/ml and 4.08 picoMol/ml respectively. The level of each tested nutrient or metabolite was not found to be statistically different between cataractous patients and controls, nor any significant trend was found to be present when the nutrients and metabolites were correlated to each other. Our results do not support the hypothesis of a nutritional deficiency in human senile cataracts. However, a defect in the antioxidative metabolism pathways could be present either systemically or at lens level.

Topics: Age Distribution; Aged; Antioxidants; Ascorbic Acid; Cataract; Erythrocytes; Female; Glutathione; Humans; Male; Malondialdehyde; Middle Aged; Risk Factors; Sex Distribution; Vitamin E

In rabbit lenses subjected to oxidative stress, induced by 1 mM diquat in vitro, there were 7- to 10-fold increases (p less than 0.001) in malondialdehyde, conjugated dienes, and carbonyl dienes, indicating extensive peroxidation of cellular membrane lipids, and approximately a 60% decrease in reduced glutathione. In the presence of 0.1-5 mM Desferal-Mn(III) these changes were diminished by 50-70%. In an experimental group of 12 rabbits having diquat-induced cataract, Desferal-Mn(III) (5% w/v) applied topically as a 50-microliters eye drop four times per day and a single intraperitoneal dose of 64 mg/kg body wt daily for 5 weeks (including pretreatment for 1 week) retarded the progression of lens opacities, whereas, in a control group of 6 rabbits treated with the vehicle (0.15 M NaCl) cataract progressed to an advanced grade. Treatment with Desferal-Mn(III) also significantly diminished production of O2.- and OH. in the lens, aqueous humor, and vitreous humor, and of H2O2 in the aqueous humor and vitreous humor. It also suppressed lipid peroxidation and oxidation of protein-SH of the lens and restored lenticular glutathione and ascorbate to normal levels.

Topics: Animals; Ascorbic Acid; Cataract; Deferoxamine; Diquat; Free Radicals; Glutathione; Hydrogen Peroxide; Hydroxides; Hydroxyl Radical; Kinetics; Lens, Crystalline; Lipid Peroxidation; Malondialdehyde; Membrane Lipids; Organ Culture Techniques; Organometallic Compounds; Rabbits

Numerous factors are related to the development of cataract. In particular the effects of free radicals as triggers for the formation of cataracts have recently attracted attention. The oxygen radicals (O2.-) produced by the hypoxanthine-xanthine oxidase system and the hydroxyl radicals (HO.) produced by Fenton reaction were measured using electron spin resonance (ESR) methods. In the present study, we investigated the effects of compounds used as anti-cataract drugs and evaluated their inhibitory effects on radical formation. Pirenoxine and ascorbic acid both caused potent suppression of the radicals.

Topics: Animals; Ascorbic Acid; Cataract; Drugs, Chinese Herbal; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; Free Radicals; Glutathione; Humans; Lens, Crystalline; Superoxides; Tiopronin

Pentosidine is a recently discovered protein crosslink, involving lysine and arginine residues linked together in an imidazo [4,5,6] pyridinium ring formed by a 5-carbon sugar during nonenzymatic browning (Maillard reaction). The presence of high ascorbate levels in the human lens and its ability to undergo nonenzymatic browning led us to investigate pentosidine formation in the aging human lens. Incubation of lens crystallins with ascorbate and its oxidation products dehydroascorbate and 2,3-diketogulonate leads progressively to the formation of pentosidine crosslinks in the presence of oxygen. Under nitrogen, however, pentosidine forms only from 2,3-diketogulonate or xylosone, a degradation product of 2,3-diketogulonate. A high correlation between pentosidine crosslinks and the degree of lens pigmentation is noted in cataractous lenses. Pentosidine is found to be primarily associated with alpha-crystallin fractions of 300-5000 kDa. These results suggest that redox imbalance in cellular senescent systems such as the ocular lens may lead to irreversible ascorbate oxidation and protein crosslinking by xylosone. This mechanism may play an important role in the pathogenesis of "brunescent" cataracts.

Topics: Adult; Aged; Aging; Animals; Arginine; Ascorbic Acid; Cataract; Cattle; Chromatography, High Pressure Liquid; Cross-Linking Reagents; Crystallins; Humans; Hydrolysis; Lens, Crystalline; Lysine; Models, Biological; Molecular Weight; Pigmentation; Reference Values

Biochemical evidence suggests that oxidative stress caused by accumulation of free radicals is involved in the pathogenesis of senile cataracts. If so, appropriate amounts of the antioxidant vitamins C and E might be expected to prevent or retard the process. Such activity has been observed in several in vitro and in vivo studies of experimentally-induced cataracts. A recent epidemiologic study found that cataract patients tended to have lower serum levels of vitamins C, E, or carotenoids than did control subjects. The present investigation, which compared the self-reported consumption of supplementary vitamins by 175 cataract patients with that of 175 individually matched, cataract-free subjects, revealed that the latter group used significantly more supplementary vitamins C and E (P = 0.01 and 0.004, respectively). Because the results suggested a reduction in the risk of cataracts of at least 50%, a randomized, controlled trial of vitamin supplementation in cataract prevention may be warranted.

Topics: Aged; Ascorbic Acid; Case-Control Studies; Cataract; Female; Humans; Interviews as Topic; Male; Middle Aged; Rural Population; Self Administration; Tea; Vitamin E

The relationship between antioxidant nutrient status and senile cataract was examined in 77 subjects with cataracts and 35 control subjects with clear lenses. Subjects with low (below the 20th percentile) and moderate (20th-80th percentiles) plasma nutrient and nutrient intake levels of vitamin C, vitamin E, and carotenoids were compared with subjects with high levels (above the 80th percentile). The odds ratio (OR) of cortical (CX) cataract among subjects with low plasma carotenoid levels was 7.2 (P less than 0.05) and the OR of posterior subcapsular (PSC) cataract for persons with low plasma vitamin C was 11.3 (P less than 0.10). Low vitamin C intake was associated with an increased risk of CX (OR = 3.7, P less than 0.10) and PSC (OR = 11.0, P less than 0.05) cataract. Subjects who consumed fewer than 3.5 servings of fruit or vegetables per day had an increased risk of both CX (OR = 5.0, P less than 0.05) and PSC cataract (OR = 12.9, P less than 0.01).

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Carotenoids; Cataract; Female; Fruit; Humans; Male; Middle Aged; Risk Factors; Vegetables; Vitamin E

Studies have been conducted to determine the efficacy of vitamin C in the prevention of cataracts induced by selenite. Administration of the latter to rat pups results in the development of advanced cataracts within 5 days. Treatment with ascorbate had a significant preventive effect. The observations indicate that selenite cataract is due to an oxidative stress to the lens. In addition, the findings are in conformity with our view that ascorbate functions as an anticataractogenic substance.

Topics: 3,4-Methylenedioxyamphetamine; Adenosine Triphosphate; Animals; Aqueous Humor; Ascorbic Acid; Cataract; Crystallins; Glutathione; Lens, Crystalline; Rats; Rats, Inbred Strains; Selenious Acid; Selenium

Topics: Aged; Antioxidants; Ascorbic Acid; Cataract; Clinical Trials as Topic; Humans; Middle Aged; Vitamin E

The effect of large intake of dietary ascorbic acid on heat-induced eye lens protein damage has been studied. Male guinea pigs of the Hartley strain were used. Ascorbic acid was administered to the experimental animals in the drinking water. The mean daily ascorbic acid intakes for the control and experimental animals were 10 and 366 mg/kg body weight, respectively. The ascorbic acid level in the lens of the experimental animals was significantly higher than in the controls, but no differences in the content of water-soluble lens proteins were observed. When a solution of water-soluble protein was incubated at 60 degrees C, insoluble aggregates were formed. The loss of water-soluble proteins from the lens of the experimental animals was significantly less than that of the controls. The results indicated that large quantities of dietary ascorbic acid were able to protect lens constituents against heat-induced damage.

Topics: Animals; Ascorbic Acid; Body Weight; Cataract; Crystallins; Diet; Guinea Pigs; Hot Temperature; Lens, Crystalline; Male

Normal and streptozotocin diabetic female Wistar rats were given vitamin C (VC) at 0.3% or 1.0% (w/w) in the diet: 1% dietary VC resulted, in 12-24 hr, in significant increases in serum ascorbate levels and lens ascorbate concentrations in normal rats. The increase was biphasic, with VC concentrations falling to a lower level which was still significantly elevated compared to controls in the period of 1.7-4 days for serum and 1.7-5 days for lenticular VC. At the end of 10 weeks the rats were examined for weight gain or loss, general body condition and cataracts. At the time of killing, blood was collected for measurement of serum glucose. Alpha-crystallin levels were determined in vitreous and aqueous humours using a radioimmunoassay. One lens from each rat was fixed for either scanning electron microscopy or light microscopy; the other lens was homogenized in 8 M guanidinium chloride for adenosine triphosphate analysis. In normal rats, a small amount of gamma-crystallin was found in the vitreous humour, and an even smaller amount in the aqueous humour. Diabetes caused a five-fold increase in the vitreous humour and a 2.5-fold increase in gamma-crystallin in the aqueous humour. Diabetes also led to a significant worsening in general body condition, loss of body weight, formation of cataracts, and decrease in lens adenosine triphosphate levels. Addition of VC to the diet of diabetic animals resulted in reduction in cataracts and a decrease of gamma-crystallin leakage into the aqueous and vitreous humours. VC had no effect on lens adenosine triphosphate levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Aqueous Humor; Ascorbic Acid; Cataract; Crystallins; Diabetes Mellitus, Experimental; Diet; Disease Models, Animal; Female; Lens, Crystalline; Rats; Rats, Inbred Strains; Vitreous Body

Examination of the opaque areas of human cortical cataracts has shown that a large portion of the opacity could be attributed to the globules found there. We tested models involving globule formation as a result of oxidative damage to rat lens cells in culture and whole chick embryo lenses. When cell monolayers from a lens cell line were exposed to oxidizing conditions they developed globules on the cell surface. The cells were protected from damage by the addition of glutathione and vitamin C. Thirteen-day chick embryo lenses were also incubated in oxidizing conditions and the amount of cellular damage was assessed using a chromium-51 release assay we have developed. After 24 hr the percent 51Cr in the medium increased by an average of 20% as a result of 10 mM hydrogen peroxide treatment. The addition of the 10 mM vitamin C to the hydrogen peroxide significantly reduced the 51Cr leakage to the control level. Light microscopy of sections of the lens showed a breakdown of the equatorial fibre arrangement in the presence of H2O2, while addition of vitamin C restored the fibre organization to almost normal. The findings suggest that oxidative stress is an important step in cataractogenesis and point towards the use of water soluble antioxidants as protective agents.

Topics: Animals; Antioxidants; Ascorbic Acid; Cataract; Cell Line; Cell Survival; Chick Embryo; Chromium Radioisotopes; Epithelium; Glutathione; Hydrogen Peroxide; Lens, Crystalline; Microscopy, Phase-Contrast; Organ Culture Techniques; Oxidation-Reduction; Rats; Vitamin E

Previous studies have suggested that free radicals and related species play a role in lens damage. The molecules involved may include proteins, lipids and DNA. Focal cortical changes and cortical liquefaction have been reported in patients with Down's syndrome over the age of 15 years. There is evidence supporting the hypothesis that trisomy 21 patients have an increase in free radical reactions and lipoperoxidation susceptibility. This could be due to an increase in the H2O2 generation catalysed by CuZn SOD although the activity of other gene products coded for on chromosome 21 cannot be excluded. Thiobarbituric acid reactive products were measured in human erythrocytes of nine DS patients and nine age-matched controls. There was a significant increase in the first group (21.0 +/- 2.3 nmol MDA/g Hb vs 16.4 +/- 2.9 nmol MDA/g Hb; p less than or equal to 0.01). In plasma, however, TBA products and antioxidant levels (ascorbic acid, tocopherol and uric acid) were not significantly different. Further studies should be carried out, namely through the use of more specific and sensitive methods, to assess the possible association between oxidative stress and cortical lens damage in DS patients.

Topics: Adolescent; Adult; Ascorbic Acid; Cataract; Child; Child, Preschool; Down Syndrome; Erythrocytes; Free Radicals; Humans; Infant; Lipid Peroxidation; Oxygen; Superoxide Dismutase; Thiobarbiturates; Uric Acid; Vitamin E

Experimental evidence suggests that oxidative stress due to the accumulation of free radicals plays a role in the pathogenesis of cataracts and that the process can be prevented or ameliorated by antioxidants. In addition, a recent study found that cataract patients tended to have lower serum levels of vitamins C, E, or carotenoids than did control subjects. This investigation, which compared the self-reported consumption of supplementary vitamins by 175 cataract patients with that of 175 individually matched, cataract-free subjects, revealed that the latter group used significantly more supplementary vitamins C and E (p = 0.01 and 0.004, respectively). Inasmuch as the observed reduction in risk of cataracts was at least 50%, a randomized, controlled trial of vitamin supplementation in cataract prevention seems justified.

Topics: Aged; Ascorbic Acid; Case-Control Studies; Cataract; Female; Humans; Male; Middle Aged; Risk Factors; Rural Population; Tea; Vitamin E

A diabetic rabbit model was developed for investigation of cataractogenesis and other changes in the anterior segment. Rabbits were fasted, injected with 0.7 mg/kg alloxan, fed 1% glucose solution for 24 hrs and returned to a normal diet. Animals showing and maintaining blood glucose of greater than 300 mg% within two days were used in this study. Concomitant with increase in blood glucose was a rise in aqueous humor glucose and osmolality, together with a decrease in ascorbate concentration. Vacuoles and small discrete opacities developed, and in some cases, at longer time periods complete opacity of anterior or posterior aspects was found. Total calcium content of the whole lens increased up to 2-fold, especially after 60 days, and was correlated with a decrease in lens transmittance of a He/Ne laser beam and also with high osmolality of the aqueous humor. Free calcium was six-fold higher in opaque areas than clear areas, and was 100-fold higher in vacuoles. It is suggested that, in addition to the recognized role in sugar cataractogenesis of osmotic stress due to sorbitol accumulation in the lens, changes of intracellular calcium in localized areas of the lens and stresses imposed by changes in aqueous humor osmolality may also be important.

Topics: Alloxan; Animals; Aqueous Humor; Ascorbic Acid; Blood Glucose; Calcium; Cataract; Diabetes Mellitus, Experimental; Lens, Crystalline; Osmolar Concentration; Rabbits; Sodium; Time Factors

Efficacy of zinc citrate ascorbate was evaluated in 146 dogs (265 eyes) that had various lens opacities. Zinc citrate ascorbate or saline placebo drops were applied topically once or twice daily for 4 to 31 weeks. Of 138 eyes treated with zinc citrate ascorbate, 86 eyes (62.3%) had no change, 48 eyes (34.8%) had increased lens opacity, and 4 eyes (2.9%) had decreased lens opacity. Of 127 eyes treated with a saline placebo, 99 eyes (77.9%) had no change, 25 eyes (19.7%) had increased lens opacity, and 3 eyes (2.4%) had decreased lens opacity. Zinc citrate ascorbate drops were not significantly (P = less than 0.05) more effective in clearing cataracts than were saline drops. Seemingly, zinc citrate ascorbate drops may have caused lens opacities to increase in area and density.

Topics: Animals; Ascorbic Acid; Cataract; Citrates; Citric Acid; Dog Diseases; Dogs; Female; Male

Investigations of aqueous humor in primary open-angle glaucoma have shown a change in its normal contents: decreased ascorbic acid in it and increased secondary products of lipid peroxidation. In patients with glaucoma of stages III and IV, a correlative relationship between them is recorded (r = -0.78). It is suggested that in the pathomechanism of increased intraocular pressure in primary glaucoma activation of the process of lipid peroxidation plays a role due to decreased concentration of ascorbic acid in the aqueous humor, being one of the most important components of antioxidative system of the eye.

Topics: Aged; Aqueous Humor; Ascorbic Acid; Cataract; Female; Glaucoma, Open-Angle; Humans; Lipid Peroxidation; Male; Middle Aged; Spectrophotometry; Thiobarbiturates

This study was of a series of the evaluation of Hachimi-Jio-Gan (Rehmannia Eight Formula, pa-wei-ti-huang-wan or Bawei dihuang wan) to the various cataracts. In this study, the drug was evaluated for its therapeutic efficacy to mouse hereditary cataract from the delay effect of cataract appearance age and the suppression rates of variation of some biochemical parameters. The dose of 200 mg of Hachimi-Jio-Gan/day/100 g of mouse body weight significantly delayed the cataract appearance age by 4 days as compared to that of non-treated group. We estimated that the delay effect of 4 days in mouse may be corresponded to 13.9 years, when it was converted into the case of human. This drug also suppressed variation of sodium and potassium ions level in the lens with cataractogenesis. Furthermore, the drug dramatically reactivated the sodium-potassium ATPase activity damaged with the cataract formation, and also had a slight action of reducing agent. From these facts, we presumed that the drug may have a prophylactic efficacy to the cataract caused by the inhibition of sodium-potassium ATPase activity and also the oxidation of lens protein.

Topics: Administration, Oral; Age Factors; Animals; Ascorbic Acid; Cataract; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Glutathione; Lens, Crystalline; Mice; Sodium-Potassium-Exchanging ATPase; Time Factors

The presence of ascorbate free radical (AFR) reductase (NADH:AFR oxidoreductase, EC 1.6.5.4) in senile cataractous human lenses was demonstrated by measuring spectrophotometrically NADH oxidation in the presence of ascorbate plus ascorbate oxidase. About 80-85% of the lens AFR reductase was probably recovered in the supernatant of the lens homogenate. Michaelis constants of the reductase were about 10 microM and less than 1 microM for AFR and NADH, respectively. We also showed that AFR reductase activities in the cataractous lenses tended to decrease with increase of insoluble lens protein contents, or showed rather the possibility that the reductase activity may have decreased before the lens protein aggregation. In the highest activity group (about 120-160 nmol NADH oxidized/min/lens), it was roughly calculated that the reductase in the lens could re-reduce immediately the total (or almost total) amount of AFR produced there by ascorbate oxidation even at a high rate of 600-800 microM/min, if NADH concentration in the lens were sufficiently maintained. The above results suggested that AFR reductase in the human lens plays important roles in ascorbate regeneration of its redox cycle, and that activity loss of AFR reductase, as well as of superoxide dismutase, glutathione peroxidase and glutathione reductase, may be responsible for the oxidative changes in lens proteins with the development of senile cataracts.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Cataract; Humans; Lens, Crystalline; NAD; NADH, NADPH Oxidoreductases; Oxidation-Reduction; Tissue Extracts

Exposure of mice to hyperbaric oxygen leads to an inhibition of the mitotic activity in the germinative epithelium of the lens. This is followed by an eventual development of cataracts. Cataracts have also been observed in human beings treated with hyperbaric oxygen for different afflictions. The lens damage and cataract formation appears to be due to in situ generation of active radicals and other active species of oxygen. These oxygen derivatives may also contribute to the multifactorial process of senile cataract formation in human beings. This hypothesis is based on in vitro experiments with rat lenses cultured in medium generating oxygen radicals, the generation of the radicals being accomplished either photochemically or enzymatically. The ability of the lens to transport rubidium and amino acids from such a medium is adversely affected. This is a recognized index of the damage to the tissue physiology. Scavengers of active oxygen species have been found to protect against this damage. Ascorbate, present in concentrations similar to that in the primate aqueous and lens, is also protective. The studies, therefore, point to an antioxidant and perhaps an anti-cataract effect of ascorbate. Pyruvate is another agent useful in this regard.

Topics: Animals; Aqueous Humor; Ascorbic Acid; Cataract; Free Radicals; Glucose; Humans; Hyperbaric Oxygenation; Lens, Crystalline; Mitosis; Oxygen; Photochemistry; Potassium Channels; Pyruvates; Pyruvic Acid; Riboflavin

The relationship between biochemical markers of antioxidant status and senile cataract was examined in 112 subjects aged 40 to 70 years. Seventy-seven of these subjects had a cataract in at least one lens. Antioxidant status was measured using erythrocyte superoxide dismutase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase activity, and indexes that included these enzymes plus plasma levels of vitamin E, vitamin C, and carotenoids. Subjects were grouped by level (low, moderate, or high) of the enzymes and antioxidant indexes. Results suggest that subjects with high levels of at least two of the three vitamins (vitamin E, vitamin C, or carotenoids) are at reduced risk of cataract relative to subjects with low levels of one or more of these vitamins (odds ratio, 0.2). The erythrocyte enzymes, either individually or in combination, did not appear to differ between subjects with and without cataract.

Topics: Adult; Aged; Ascorbic Acid; Carotenoids; Catalase; Cataract; Female; Glutathione Peroxidase; Humans; Male; Middle Aged; Reference Values; Superoxide Dismutase; Vitamin E; Vitamins

Topics: Ascorbic Acid; Cataract; Dehydroascorbic Acid; Electron Spin Resonance Spectroscopy; Humans; Lens, Crystalline; Oxidation-Reduction; Spectrometry, Fluorescence

Lens retrodots are round, oblong, or oval features in the perinuclear zone of the adult lens after the fifth decade of life and associated with cataract. Retrodots were found in 47 out of 121 eyes with cataract (39%) in the present series. They show birefringence in vivo and in vitro, and chemical studies suggest that they contain calcium oxalate. It is proposed that ascorbic acid, which is abundant in the normal human lens, is the most likely source for this oxalate. Ascorbic acid is thought to have a protective role against oxidative stress in the lens and other parts of the eye, and its level is known to be reduced in senile cataract. The presence of the retrodots may identify lenses which have been exposed to oxidative stress and are less capable of resisting oxidative damage.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Birefringence; Calcium Oxalate; Cataract; Humans; Lens Cortex, Crystalline; Lens Nucleus, Crystalline; Lens, Crystalline; Middle Aged

Topics: Adult; Ascorbic Acid; Cataract; Dehydroascorbic Acid; Electron Spin Resonance Spectroscopy; Humans; Lens, Crystalline; Male; Oxidation-Reduction

Blood, aqueous humor and cataracts obtained from an Indian population were analyzed for ascorbic acid content. While the concentrations of ascorbic acid in the blood and cataracts were similar in patients with cortical and nuclear cataracts, the level of this nutrient was lower in the aqueous humor of patients with cortical cataracts. This suggests a sluggish transport of ascorbate from the blood to the aqueous humor in the latter group. It is possible that this lower level of ascorbate might be one of the factors participating in cataractogenesis. The lower aqueous ascorbate in the group with the cortical cataracts could not be accounted for by any dietary deficiency of this nutrient. Hence, it appears metabolically related.

Topics: Age Factors; Aged; Aqueous Humor; Ascorbic Acid; Cataract; Humans; Middle Aged

Topics: Ascorbic Acid; Cataract; Humans; Lens, Crystalline; Solutions; Spectrometry, Fluorescence

The fluorescence spectra of nucleus and cortex material from human lenses obtained as a result of extracapsular cataract extraction were observed. With advancing cataract formation the fluorescence spectra changed in a very characteristic way. The changes in ascorbic acid were compared with those caused by cataract development. Clinical application of corresponding measuring instruments would appear to make sense.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Cataract; Cataract Extraction; Female; Humans; Lens Cortex, Crystalline; Lens Nucleus, Crystalline; Male; Spectrometry, Fluorescence

Topics: Animals; Ascorbic Acid; Cataract; Citrates; Dog Diseases; Dogs; Drug Combinations; Humans; Zinc

The level of lipid peroxide (LPO) in glucocorticoid-induced cataractous lenses was measured by using thiobarbituric acid. When 0.25 mumol of hydrocortisone hemisuccinate sodium (HC) were administered to 15-day-old chick embryos, the level of LPO in the lens increased to approximately 1.4-fold of the control level at 24 to 48 hr after HC treatment. However, the level returned to the control level by 96 hr with the disappearance of opacity in the lens. A triple application of ascorbic acid (20 mumol/egg) at 3, 10 and 20 hr after HC treatment prevented cataract formation and elevation in the level of LPO in 60% of the lenses. In 40% of the eggs treated with HC plus ascorbic acid, the results were no different than HC alone. Treatment with prednisolone hemisuccinate sodium (0.25 mumol/egg) produced an elevation in the level of LPO in the lens but that with cortisone hemisuccinate sodium or cortexolone hemisuccinate sodium did not change the level of LPO in the lens. The phenomena of the cataract formation and the elevation of LPO in the lens caused by HC seemed to be related to each other and due to its glucocorticoid activities.

Topics: Animals; Ascorbic Acid; Cataract; Chick Embryo; Cortisone; Cortodoxone; Glucocorticoids; Hydrocortisone; Lens, Crystalline; Lipid Peroxides; Prednisolone

The reductone ascorbic acid, present in the crystalline lens in concentrations higher than those of glucose, is capable of undergoing nonenzymatic "browning" in the presence of lenticular proteins. We studied the nonenzymatic browning with ascorbate in model systems employing bovine serum albumin and lens crystallins. When bovine serum albumin, alpha-crystallin, or gamma-crystallin was incubated with [14C]ascorbic acid, the formation of yellow and then brown condensation products appeared to correlate with increasing protein-associated radioactivity. The fluorescence spectrum of these products was similar to that of homogenates of human cataractous lenses. We suggest that the nonenzymatic reaction of lens crystallins with ascorbic acid may contribute, at least in part, to the color changes of aging lenses and to the physical lenticular deterioration leading to senile cataract. High dietary intake of ascorbic acid did not affect the fluorescence spectrum of murine lenses; thus, we assume that the speed and extent of the lenticular browning reactions must depend on a deterioration of other factors of the multicomponent antioxidant system of the eye.

Topics: Anaerobiosis; Animals; Antioxidants; Ascorbic Acid; Carbohydrate Metabolism; Cataract; Crystallins; Fluorescence; Free Radicals; Glutathione Reductase; Humans; Mice; Oxidation-Reduction; Serum Albumin, Bovine

High-performance liquid chromatography on a Supelcosil LC-HN2 analytical column in weak anion exchange mode has allowed separation of ascorbic acid, in less than 5 min, from other interfering substances in serum and aqueous humour. UV monitoring at 254 nm enables ascorbic acid to be detected at 20 pmol level. A method for determination of ascorbic acid concentration in serum and aqueous humour is described, and values from 10 cataract patients are reported.

Topics: Aged; Aqueous Humor; Ascorbic Acid; Cataract; Chromatography, High Pressure Liquid; Female; Humans; Male; Middle Aged

Serum, aqueous humour, and lens ascorbic acid levels were determined by high-performance liquid chromatography in cataract-, closed-angle glaucoma-, and aphakic patients. The total number of 108 patients were subdivided into different groups. In several groups the pre-operative serum and aqueous amounts were tested, whereafter patients in some groups were loaded with ascorbic acid orally. Finally, a second test was performed on samples taken during operation. It turned out that the ascorbic acid concentration mechanism in cataractous eyes needed more than 12 h for maximum reaction on the loading stimulus. The slow reaction is surprising compared to other species, and it may reflect an affection of the secretory process itself in this disease.

Topics: Aged; Aphakia, Postcataract; Aqueous Humor; Ascorbic Acid; Cataract; Cataract Extraction; Chromatography, High Pressure Liquid; Female; Glaucoma; Humans; Lens, Crystalline; Male; Middle Aged; Time Factors

Glucocorticoid administration to developing chick embryos is known to promote cataract formation with a decreasing level of glutathione in the lens. To gain further understanding of this process, the level of ascorbic acid, a biological antioxidant, in the lenses was measured during the course of glucocorticoid treatment. When 0.25 mumol of hydrocortisone hemisuccinate sodium (HC) were administered to 15-day-old chick embryos, the level of ascorbic acid in the lens began to decline after 30 hr and became around 40% of the control value at 48 hr after HC treatment. At this time about 90% of the lenses showed opacity in the nuclear region. However, the level of ascorbic acid in the cataractous lens recovered to the control level at 96 hr, a time when the lens has recovered from cataract formation. A triple application of ascorbic acid (20 mumol/egg) at 3, 10 and 20 hr after HC treatment significantly prevented lens opacification. The administration of ascorbic acid prevented the decline of ascorbic acid content and partially that of glutathione content in the lens caused by HC.

Topics: Animals; Ascorbic Acid; Cataract; Chick Embryo; Glutathione; Hydrocortisone; Lens, Crystalline

The purpose of the present investigation was to determine the concentration of ascorbate in the aqueous humor of guinea pigs over a 1-year period following the cutaneous application of a potential cataractogenic agent, acetone. Forty young guinea pigs received 15 ml acetone in small doses on their backs over a 6-week period; the ascorbate in their aqueous humor did not increase above 10 mg/100 ml during a 1-year test period. Ten control animals received only saline on their backs and the ascorbate concentrations steadily increased from 12 to over 18 mg/100 ml during the same time period. Three months after acetone treatment 12 animals (30%) developed cataracts and their ascorbate levels dropped to below 9 mg/100 ml after 1 year.

Topics: Acetone; Animals; Aqueous Humor; Ascorbic Acid; Cataract; Guinea Pigs

Topics: Adult; Aged; Aqueous Humor; Ascorbic Acid; Cataract; Female; Humans; Male; Middle Aged

Topics: Aged; Amino Acids; Ascorbic Acid; Cataract; Drug Combinations; Humans; Inositol; Iodine; Pyridoxine

Exposure of rat lens to fluorescent daylight (150 ft candles) under tissue culture conditions led to a substantial lipid peroxidation as evidenced by the formation of malonaldehyde (MDA). MDA content of lenses incubated overnight in presence of such light was approximately sixfold of that in the control lenses cultured in the dark. These cultures were maintained in physiological medium resembling aqueous humor which does not contain any additional photoactive component. Thus, the lens in its physiological surroundings is susceptible to photoperoxidation by light of wavelengths which freely penetrate the eye. Photoperoxidation could be thwarted by superoxide dismutase, catalase, and ascorbate, suggesting that the observed peroxidative degradation is initiated by photocatalytic generation of superoxide and its subsequent derivation to other potent oxidants. These studies provide for the first time suggestive evidence that senile cataract development may in part be linked to the in vivo photochemical generation of superoxide and other potent oxidants in the aqueous humor and lens derived from the ambient oxygen and light; and ascorbate which is maintained at high levels in this fluid by virtue of its active transport from plasma, is physiologically important in preventing the deleterious action of these potent oxidants. The studies thus indicate for the first time the possibilities of a hitherto unrecognized role of ascorbate against cataracts and other age-, light- and oxygen-dependent ocular abnormalities, In addition, the study re-emphasizes the role of tissue catalase and superoxide dismutase in the prevention of photoperoxidative damages to the tissue.

Topics: Animals; Ascorbic Acid; Catalase; Cataract; Culture Techniques; Lens, Crystalline; Light; Lipid Peroxides; Malondialdehyde; Rats; Rats, Inbred Strains; Superoxide Dismutase

Topics: Adolescent; Adult; Aged; Animals; Aotus trivirgatus; Aqueous Humor; Ascorbic Acid; Cataract; Cattle; Child; Child, Preschool; Female; Humans; Hydrogen Peroxide; In Vitro Techniques; Lens, Crystalline; Macaca mulatta; Male; Middle Aged

Studies on the ultraviolet ray absorption in the aqueous humour of rabbit, cat, monkey, guinea pig, and rat showed marked species differences. In the rabbit aqueous the ascorbic acid, the proteins, and some amino acids (tyrosine, phenylalanine, cystine, and tryptophane) are together responsible for the total absorption, and a very great part of it refers to the ascorbic acid content. Accordingly, species with significant amounts of ascorbic acid in the aqueous (monkey, rabbit, guinea pig) have a greater absorption capacity towards ultraviolet radiation than species (cat, rat) lacking this substance. This effect of the ascorbic acid may contribute in protecting the lens against the most biotoxic ultraviolet rays. It seems that the ascorbic acid concentration is highest in the aqueous of typical day animals and lowest in species being active in the dark, indicating a correlation between the aqueous' ascorbic acid level and the quantity of incident light on the eye. The possible significance of changed aqueous ultraviolet ray absorption in the pathogenesis of human cataract development is discussed.

Topics: Animals; Aqueous Humor; Ascorbic Acid; Cataract; Cats; Cercopithecus; Guinea Pigs; Haplorhini; Humans; Rabbits; Rats; Ultraviolet Rays

Topics: Animals; Ascorbic Acid; Cataract; Dogs; Epithelium; Lens, Crystalline; Microwaves; Rabbits; Radiation Dosage

1. Activities of superoxide dismutase (superoxide: superoxide oxidoreductase, EC 1.15.1.1) have been estimated in eye tissues. In rabbit eye, superoxide dismutase is present in corneal epithelium, corneal endothelium, lens, iris, ciliary body and retina. In lens the activity is in capsule epithelium. 2. Copper chelator diethyldithiocarbamate inhibited lens superoxide dismutase in vitro and in vivo in rabbit. 3. H2O2 caused inhibition of superoxide dismutase activity of lens extract, and this inhibition was potentiated by the catalase inhibitor 3-amino-1H-1,2,4-triazole (3-aminotriazole) or NaN3. 3-Aminotriazole or NaN3 had no effect on lens superoxide dismutase. Thus endogenous catalase of lens affords protection to the lens superoxide dismutase from inactivation by H2O2. 4. In rabbit having early cataract (vacuolar stage) induced by feeding-3-aminotriazole, there was a decrease in superoxide dismutase of lens, a fall in ascorbic acid of ocular humors and lens, and a 2--3-Fold increase in H2O2 of aqueous humor and vitreous humor. We conclude that catalase of eye affords protection to the lens from H2O2 and it also protects superoxide dismutase of lens from inactivation by H2O2. Superoxide dismutase, in turn, protects the lens from the superoxide radical, O2.-. It is likely that inhibition of these enzymes may lead to production of the highly reactive oxidant, the hydroxyl radical, under pathological conditions when H2O2 concentration in vivo exceeds physiological limits as in cataract induced by 3-aminotriazole. A scheme of reaction mechanism has been proposed to explain the relative functions of ocular catalase and superoxide dismutase. Such a mechanism may be involved in cataractogenic process in the human.

Topics: Amitrole; Animals; Ascorbic Acid; Catalase; Cataract; Ditiocarb; Eye; Female; Humans; Hydrogen Peroxide; In Vitro Techniques; Lens, Crystalline; Male; Ocular Physiological Phenomena; Rabbits; Superoxide Dismutase; Superoxides

Topics: Adult; Aged; Ascorbic Acid; Cataract; Female; Glutathione; Humans; Lens, Crystalline; Male; Middle Aged

Because the dietary requirement for ascorbic acid is similar in humans and guinea pigs, galactose-induced cataract research with the guinea pig as an experimental model instead of the rat might be appropriate and may represent a closer analogy to galactosemic cataract formation in humans. In this study, dietary ascorbic acid was found in all guinea pigs to have a retarding or delaying effect on the development of galactose-induced cataracts.

Topics: Animals; Ascorbic Acid; Cataract; Diet; Disease Models, Animal; Galactosemias; Guinea Pigs

I have discussed five aspects of lens metabolism and their possible relationship to cataract in man, and this has left me with five fundamental questions to be answered. 1. Are the fluorescent tryptophan derivatives, found only in the lens of man and higher primates, involved in the development of brown nuclear cataract? 2. Is naphthalene cataract in rabbits a model for any type of cataract in man--i.e., are quinones ever formed in the human eye? 3. Is diabetes the only cataract in which osmotic swelling is important? 4. Does self-digestion of protein in the human lens contribute to cataract development? 5. Are the consequences of the abnormal maturation of lens fibers, which occurs in tryptophan deficiency cataract in rats, ever seen in man?

Topics: Aging; Animals; Ascorbic Acid; Cataract; Crystallins; Diabetic Retinopathy; Humans; Lens, Crystalline; Naphthalenes; Naphthoquinones; Peptide Hydrolases; Sorbitol; Tryptophan

Topics: Adolescent; Adult; Age Factors; Aged; Aqueous Humor; Ascorbic Acid; Cataract; Humans; Lens, Crystalline; Middle Aged

Topics: Adult; Age Factors; Aged; Ascorbic Acid; Cataract; Eye; Humans; Middle Aged; Morphine; Time Factors; Tissue Extracts; Visual Acuity

Topics: Age Factors; Anemia, Hemolytic, Congenital Nonspherocytic; Animals; Ascorbic Acid; Black People; Blood Transfusion; Catalase; Cataract; Cats; Cattle; Dogs; Erythrocytes; Female; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Haplorhini; Humans; Hydrogen Peroxide; Lens, Crystalline; Oxygen Consumption; Pregnancy; Rabbits; Triazoles

Topics: Animals; Aqueous Humor; Ascorbic Acid; Cataract; Free Radicals; Glutathione Reductase; Herbicides; Hydrogen Peroxide; Lens, Crystalline; Light; NADP; Oxidation-Reduction; Pyridines; Rats; Vitreous Body

Topics: Animals; Aqueous Humor; Ascorbic Acid; Cataract; Diet; Glutathione; In Vitro Techniques; Lens, Crystalline; Naphthalenes; Naphthoquinones; Rabbits; Vitreous Body

Topics: Animals; Aqueous Humor; Ascorbic Acid; Carbon Isotopes; Cataract; Diet; Epithelium; Glutathione; Herbicides; Intestinal Absorption; Lens, Crystalline; Mitosis; Proteins; Pyridines; Rats; Vitreous Body

Topics: Animals; Ascorbic Acid; Cataract; Free Radicals; Glutathione; Herbicides; In Vitro Techniques; Pyridines; Rats

Oxidation of tyrosine in the presence of bovine lens proteins leads to the formation of brown or black melanoproteins. Both tyrosinase and the oxidizing system of ferrous sulphate-ascorbic acid-EDTA are effective. The fluorescence of the lens proteins is both altered and enhanced by the tyrosine-oxidizing systems. Their fluorescence spectra resemble those of urea-insoluble proteins of human cataractous lens and of 1,2-naphthaquinone-proteins of naphthalene cataract. The lens proteins lose their thiol groups and, in acid hydrolysates of treated beta-and gamma-crystallins, a substance has been detected chromatographically that behaves similarly to a compound formed when 3,4-dihydroxyphenylalanine (dopa) is oxidized by tyrosinase in the presence of cysteine. Analysis and behaviour of this substance from hydrolysates of lens proteins suggest that it is a compound of cysteine and dopa.

Topics: Animals; Ascorbic Acid; Cataract; Catechol Oxidase; Cattle; Chemical Phenomena; Chemistry; Chromatography, Paper; Crystallins; Cysteine; Dihydroxyphenylalanine; Edetic Acid; Fluorescence; Iron; Naphthoquinones; Oxidation-Reduction; Proteins; Sulfates; Sulfur; Tyrosine

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Cataract; Child; Child, Preschool; Female; Humans; Lens, Crystalline; Male; Middle Aged; Oxidation-Reduction

Topics: Ascorbic Acid; Cataract; Glaucoma; Humans; Injections, Intravenous; Intraocular Pressure; Male; Mannitol; Middle Aged; Time Factors

Topics: Ascorbic Acid; Cataract; Glutathione; Humans; Lens, Crystalline

Topics: Adolescent; Amino Acid Metabolism, Inborn Errors; Amino Acids; Ascorbic Acid; Cataract; Female; Humans; Intellectual Disability; Mandelic Acids; Methionine; Mixed Function Oxygenases; Phenylacetates; Phenylpyruvic Acids; Tyrosine

Topics: Adult; Aqueous Humor; Ascorbic Acid; Cataract; Eye Diseases; Humans; India; Lens, Crystalline

Topics: Animals; Ascorbic Acid; Cataract; Chickens; Dinitrophenols; Female; Glutathione; Male

Topics: Ascorbic Acid; Cataract; Glaucoma; Glycerol; Humans; Injections, Intravenous; Intraocular Pressure; Mannitol; Urea

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Aqueous Humor; Ascorbic Acid; Aspartate Aminotransferases; Blood Cell Count; Blood Glucose; Blood Proteins; Blood Urea Nitrogen; Body Weight; Cataract; Cholesterol; Eosinophils; Eye; Fructose-Bisphosphate Aldolase; Intraocular Pressure; L-Lactate Dehydrogenase; Lens, Crystalline; Leukocytes; Potassium; Proteins; Rabbits; Triamcinolone Acetonide

Topics: Animals; Ascorbic Acid; Cataract; Intraocular Pressure; Lens, Crystalline; Microwaves; Rabbits; Radiation Injuries, Experimental; Water-Electrolyte Balance

Topics: Aqueous Humor; Ascorbic Acid; Bicarbonates; Blood Chemical Analysis; Cataract; Chemical Phenomena; Chemistry; Chlorides; Eye Diseases; Glucose; Humans; In Vitro Techniques; Lactates; Manometry

Topics: Aged; Ascorbic Acid; Cataract; Cysteine; Female; Humans; Male; Middle Aged; Riboflavin

Topics: Aqueous Humor; Ascorbic Acid; Asian People; Blood Chemical Analysis; Cataract; Humans; India; Water

Topics: Ascorbic Acid; Capillary Permeability; Cataract; Cataract Extraction; Dexamethasone; Humans; Ophthalmologic Surgical Procedures; Ophthalmology; Skin Tests; Vitamins

Topics: Acetazolamide; Ascorbic Acid; Cataract; Folic Acid; Humans; Vitamin B Complex; Vitamins

Topics: Ascorbic Acid; Cataract; Dehydroascorbic Acid; Disease; Eye; Humans; Inflammation; Uvea

Topics: Aqueous Humor; Ascorbic Acid; Blood; Cataract; Humans; Vitamins

Topics: Aqueous Humor; Ascorbic Acid; Cataract; Ciliary Body; Lens, Crystalline; Plasma

Topics: Ascorbic Acid; Cataract; Dehydroascorbic Acid; Diabetes Mellitus; Humans; Vitamins

Topics: Ascorbic Acid; Cataract; Humans; Vitamins