ascorbic-acid and Diabetic-Retinopathy

To investigate the associations between circulating micronutrients (vitamins A, C, D, E, and carotenoids) and risk of diabetic retinopathy (DR).. Cross-sectional study and meta-analysis.. The cross-sectional study included 517 diabetic participants aged ≥40 years in the 2005-2006 National Health and Nutrition Examination Survey. Serum vitamin D was converted to liquid chromatography-tandem mass spectrometry-equivalent results, while other micronutrients were measured using high-performance liquid chromatography. Presence of DR was determined based on non-mydriatic fundus photographs. A meta-analysis was subsequently performed, which included relevant studies published from January 01, 1990 to December 31, 2020.. Of the 517 included participants, DR was identified in 159 participants (25.17%). After adjusting for multiple confounders, only serum vitamin C was associated with a lower risk of DR (odds ratio [OR]: 0.60; 95% confidence interval [CI]: 0.38-0.95). A total of 35 studies were included in the subsequent meta-analysis. Comparing 1056 participants with DR to 920 controls, the pooled weighted mean difference (WMD) of vitamin C was -11.01 (95% CI: -19.35 to -2.67). Regarding vitamins D and E, the pooled WMD was -3.06 (95% CI: -5.15 to -0.96) and -3.03 (95% CI: -4.24 to -1.82), respectively. No associations were identified between DR and circulating vitamin A or carotenoids.. Lower levels of circulating vitamins C, D, and E were found in DR patients than those without. More high-quality studies are required to assess the real effects of micronutrients on DR.

Topics: Ascorbic Acid; Carotenoids; Cross-Sectional Studies; Diabetes Mellitus; Diabetic Retinopathy; Humans; Micronutrients; Nutrition Surveys; Risk Factors; Vitamins

Since the retina continuously receives light to enable vision, reactive oxygen species (ROS) are easily generated in neural retina. The oxidative stress induced by ROS may be involved in the onset and progression of blinding aging diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Although supply of antioxidants to the retina is important to maintain the redox homeostasis in neural retina, the blood-retinal barrier (BRB) is created by complex tight-junctions of retinal capillary endothelial cells and retinal pigment epithelial cells to prevent the free diffusion of substances. The BRB is equipped with several membrane transporters to supply nutrients and essential molecules including antioxidants and drugs which exhibit antiaging effect to the retina from the circulating blood. In this review, the transporter-mediated retinal distribution of key endogenous compounds and drugs, such as vitamin C, l-cystine and gabapentin, is introduced for antiaging of the retina.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood-Retinal Barrier; Cystine; Diabetic Retinopathy; Endothelial Cells; Gabapentin; Glaucoma; Homeostasis; Humans; Macular Degeneration; Oxidation-Reduction; Oxidative Stress; Rats; Reactive Oxygen Species; Retina; Tight Junctions

Macular edema poses a significant risk for visual loss in persons with diabetic retinopathy. It occurs when plasma constituents and fluid leak out of damaged retinal microvasculature in the area of the macula, causing loss of central vision. Apoptotic loss of pericytes surrounding capillaries is perhaps the earliest feature of diabetic vascular damage in the macula, which is also associated with dysfunction of the endothelium and loss of the otherwise very tight endothelial permeability barrier. Increased oxidative stress is a key feature of damage to both cell types, mediated by excess superoxide from glucose-induced increases in mitochondrial metabolism, as well as by activation of the receptor for advanced glycation end products (RAGE). The latter in turn activates multiple pathways, some of which lead to increased oxidative stress, such as those involving NF-ĸB, NADPH oxidase, and endothelial nitric oxide synthase. Such cellular oxidative stress is associated with low cellular and plasma ascorbic acid levels in many subjects with diabetes in poor glycemic control. Whether repletion of low ascorbate in retinal endothelium and pericytes might help to prevent diabetic macular edema is unknown. However, cell culture studies show that the vitamin prevents high-glucose and RAGE-induced apoptosis in both cell types, that it preserves nitric oxide generated by endothelial cells, and that it tightens the leaky endothelial permeability barrier. Although these findings need to be confirmed in pre-clinical animal studies, it is worth considering clinical trials to determine whether adequate ascorbate repletion is possible and whether it might help to delay or even reverse early diabetic macular edema.

Topics: Apoptosis; Ascorbic Acid; Diabetic Retinopathy; Endothelium; Humans; Macular Edema; Nitric Oxide; Oxidative Stress; Retina; Superoxides

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

We have evaluated the evidence for the association between intake and blood levels of micronutrients and diabetic retinopathy. Treatment for diabetic retinopathy requires significant clinical input and specialist ophthalmologic care. Micronutrients, including vitamin C, vitamin E, and magnesium, may interfere with pathologic mechanisms of diabetic retinopathy and potentially alter its risk.. We conducted a search of epidemiologic literature in PubMed and Embase from 1988 to May 2008, using keywords for exposures, including magnesium, ascorbic acid, alpha-tocopherol and antioxidants, and outcomes, including diabetic retinopathy. Two authors independently extracted data and assessed the quality of the studies using the Newcastle-Ottawa Scale. The overall quality of evidence was graded as I (highest), II, or III (lowest).. Of the 766 studies identified, we reviewed 15 studies, comprising 4094 individuals. For vitamin C, hospital-based studies reported an inverse association between plasma levels with retinopathy, whereas population-based studies showed no association between dietary intake and retinopathy. For vitamin E, there was no association with dietary intake or plasma levels and retinopathy. For magnesium, a single prospective analysis showed an association between low levels in plasma and progression of retinopathy, but cross-sectional studies reported inconsistent results. In the assessment of quality, population-based studies had higher ratings than hospital-based studies.. The evidence suggests that dietary intake or plasma levels of vitamins C and E and magnesium do not seem to be associated with diabetic retinopathy. Because of differences in study designs and measurement of micronutrients, incomplete ascertainment of retinopathy, and residual confounding, these findings require confirmation.. The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; Diabetic Retinopathy; Diet; Humans; Magnesium; Micronutrients

There is increasing evidence that diabetic retinopathy is caused by the action of free radicals. Radical scavengers like vitamin C and superoxide dismutase (SOD) may influence the outcome and progression of diabetic retinopathy, but no systematic review of the literature has been published to examine this hypothesis.. The aim of the current research was to review the literature in a standard systematic way in order to assess the effects of vitamin C and superoxide dismutase on diabetic retinopathy in methodologically robust trials.. We tried to obtain studies from computerised searches of MEDLINE, EMBASE, CINAHL, Web of Science and The Cochrane Library.. Only randomized clinical trials (RCTs) that evaluated the effect of vitamin C, superoxide dismutase or both in the treatment of diabetic retinopathy were considered.. Two authors independently read all abstracts, titles or both and wanted to assess risk of bias and to perform data extraction. Discrepancies were planned to be resolved by consensus or by the judgement of a third author.. A total of 241 publications were identified by the electronic searches. Of these, 28 were identified as potentially containing information about the treatment of patients with diabetic retinopathy using vitamin C or SOD and were read in full. No trial evaluated the treatment of diabetic retinopathy with vitamin C or SOD.. No research to date has adequately examined the treatment of diabetic retinopathy with vitamin C or SOD in such a way as to indicate whether this form of intervention has a significant impact on the progress of this clinical condition. The potential role of these substances in the treatment of diabetic retinopathy remains open to debate, and it is suggested that future research focusing on patient-oriented outcomes should address this important issue.

Topics: Ascorbic Acid; Diabetic Retinopathy; Free Radical Scavengers; Humans; Superoxide Dismutase

Topics: Animals; Antioxidants; Ascorbic Acid; Controlled Clinical Trials as Topic; Diabetic Retinopathy; Glycosylation; Humans; Lipid Peroxidation; Rats; Sorbitol; Vitamin E

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Corneal Diseases; Diabetic Retinopathy; Drug Therapy, Combination; Eye; Eye Burns; Eye Diseases; Humans; Tuberculosis, Ocular; Vision, Ocular

Topics: Anabolic Agents; Anticoagulants; Ascorbic Acid; Calcium Dobesilate; Clofibrate; Cryosurgery; Diabetic Retinopathy; Humans; Hypoglycemic Agents; Hypophysectomy; Light Coagulation; Salivary Glands; Sclera

To study the effects of anti-oxidant on tear film parameters in patients with diabetes mellitus, a total of 100 patients of diabetes mellitus with defective Schirmer test and tear film break-up time were enrolled in this study and they were given vitamin C (1000 mg/day) and vitamin E (400 IU/day) for 30 days. Schirmer test and tear break-up, time were re-examined after 1 month. There was significant improvement in values for Schirmer test (p < 0.001) and tear break-up time. Oxidative stress has an influence on how diabetes mellitus affects various systems of body. This study clearly depicted im- portant roles of vitamins C and E in improving the well-being of the ocular surface.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Conjunctiva; Diabetic Retinopathy; Female; Humans; Male; Middle Aged; Tears; Treatment Outcome; Vitamin E

The hypoglycemic drug, troglitazone (TGZ) has antioxidant activity. Superoxide dismutase (SOD) removes superoxide produced by cells. We measured the response of SOD-like activity (deltaSOD) to ascorbic acid (AA) or TGZ using electron spin resonance at various glucose concentrations in polymorphonuclear leukocytes from 18 type 2 diabetic patients and 18 healthy controls. In control and diabetic subjects, ASOD in response to AA was dose-dependent (maximal effect at 100 ng/ml). Maximal response occurred 2 min after AA addition (50 ng/ml). In cells from diabetic patients, ASOD with 25 ng/ml AA was significantly less than for healthy controls. The deltaSOD with AA changed little at glucose concentration from 0 to 200 mg/dl. In patient and control cells, higher glucose concentrations (400 to 800 mg/dl) reduced ASOD with AA. Response patterns with TGZ resembled those with AA. deltaSOD with AA correlated positively with glycosylated hemoglobin A1c.. The present data suggest that an amerioration of blood glucose on high levels in diabetic patients plays an important role in an antioxidant efficacy of TGZ and AA on leukocytes in patients.

Topics: Aged; Albuminuria; Antioxidants; Ascorbic Acid; Chromans; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Retinopathy; Dose-Response Relationship, Drug; Electron Spin Resonance Spectroscopy; Female; Glucose; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Leukocytes; Male; Middle Aged; Superoxide Dismutase; Thiazoles; Thiazolidinediones; Troglitazone

Topics: Adult; Aged; Ascorbic Acid; Capillary Fragility; Diabetes Mellitus; Diabetic Retinopathy; Diet Therapy; Humans; Middle Aged; Placebos; Pressure; Time Factors

Diabetic retinopathy (DR) is a common complication of diabetes with nocuous effects on patients' eye health, typically accompanies by excessive inflammation and oxidative stress. Insulin-like growth factor-2 messenger RNA-binding protein 3 (IGF2BP3) was engaged with inflammation, whereas its precise role in the DR process was unclear. And enhanced lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and decreased ascorbic acid (AA) were also found in DR. This study was to explore the regulatory role and mechanism of IGF2BP3, MALAT1 and AA in the high glucose (HG)-induced retinal pigment epithelial (RPE) cell injury.. ARPE-19 cells were treated with HG to establish the in vitro RPE cell injury model. The mRNA and protein levels of the gene were evaluated by qRT-PCR or Western blot. Immunofluorescence detected the translocation condition of the p65 protein. Inflammatory factor levels were detected by ELISA assays. Apoptosis was detected by flow cytometry. The binding interaction of IGF2BP3 and MALAT1 was validated by RIP-qPCR assays.. In HG-induced RPE cell injury, IGF2BP3 expression, inflammatory response and apoptosis were enhanced. Next, the IGF2BP3 activated the NF-κB signalling to promote the RPE cell injury development. MALAT1 could directly bind with IGF2BP3 and up-regulate its expression. In addition, AA ameliorated the HG-induced RPE cell injury through the regulation of MALAT1.. Ascorbic acid ameliorated HG-induced RPE cell injury by repressing the NF-κB signalling pathway via modulating the MALAT1/IGF2BP3 axis.

Topics: Ascorbic Acid; Cell Line; Diabetic Retinopathy; Epithelial Cells; Glucose; Humans; Inflammation; NF-kappa B; Retinal Pigments; RNA, Long Noncoding; Signal Transduction

Diabetic retinopathy (DR) is a worldwide health problem, and intravitreal injections of anti-inflammatory and antiangiogenic agents represent the leading therapy to effectively treat DR and its complications. However, they are expensive, invasive, and stressful for patients. This study aims to demonstrate that statins and vitamin C (alone or in combination with statins) as complementary therapy could have an impact on the nonproliferative DR (NPDR) complication rate.. A retrospective review was conducted with 479 patients with NPDR. Statins and vitamin C intake were analyzed, along with the rate of diabetic macular edema (DME), vitreous hemorrhage (VH), circinate maculopathy (CM), and proliferative DR (PDR).. Lower DME (P = .07) and VH (P = .018) rates were observed in patients who took statins compared with those who were statin-naïve. This difference was significant after accounting for vitamin C intake, with a lower rate of DME (P = .01) and VH (P = .008) in patients with statin-vitamin C combination therapy.. Statins, alone or with vitamin C, appear to reduce the complication rate of NPDR. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:S23-S27.].

Topics: Aged; Antioxidants; Ascorbic Acid; Diabetic Retinopathy; Disease Progression; Drug Therapy, Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Retina; Retrospective Studies; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity

Vitreous vitamin C, as an anti-oxidant, is responsible for regulating oxygen tension and oxidative stress in the eye. Oxidative stress and retinal ischemia are implicated in the development of proliferative diabetic retinopathy (PDR). In this study, we aimed to determine whether vitreous level of vitamin C is compromised in patients with PDR and to investigate the association of diabetic macular ischemia and vitamin C.. This prospective study enrolled forty patients who underwent pars plana vitrectomy for the treatment of PDR (PDR group, n = 20) and idiopathic epiretinal membrane (control group, n = 20). Serum, aqueous humor, and the vitreous were collected for the analysis of vitamin C level by HPLC. Diabetic macular ischemia (DMI) in PDR group was evaluated with fluorescein angiography (FA).. PDR patients (60.4 ± 2.1 y) were younger than non-diabetic control patients (67.4 ± 1.2 y). Serum, aqueous, and vitreous levels of vitamin C in PDR were 38.7%, 22.5%, and 11.1% of non-diabetic control group, respectively. All PDR patients had DMI (grade 1: 25%, grade 2: 30%, grade 3: 30%, grade 4: 15%). DMI grade was inversely correlated with the level of vitreous vitamin C (r = -0.546, P = 0.019), not with HbA1C, serum, or aqueous vitamin C level. In addition, the level of vitreous vitamin C (4.5 ± 2.6 μg/ml) in high DMI group (Gr 3 &4) was lower than that (31.0 ± 9.1 μg/ml) in low DMI group (Gr 1&2) (P = 0.015).. Vitreous level of vitamin C in PDR patients showed a tenfold decrease, which was associated with the degree of macular ischemia. This suggests that vitreous vitamin C depletion may cause macula ischemia in PDR patients.

Topics: Aged; Antioxidants; Aqueous Humor; Ascorbic Acid; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Epiretinal Membrane; Female; Humans; Male; Middle Aged; Oxidative Stress; Vitrectomy; Vitreous Body

Diabetic retinopathy (DR) is a serious microvascular complication of diabetes and a major cause of blindness in the developing world. Early diabetic retinopathy is characterized by a loss of pericytes and vascular endothelial cells, a breakdown of the blood-retinal barrier, vascular dysfunction and vascular-neuroinflammation. However, optimal treatment options and related mechanisms are still unclear. MicroRNA-126 (miR-126) plays a potential role in the pathogenesis in DR, which may regulate VEGF, Ang-1 and VCAM-1 expressions. This study investigated the therapeutic effects and mechanisms of Niaspan treatment of DR in diabetes (DM) rats. DM rats exhibits significantly decreased miR-126 and tight junction Claudin-5/Occludin/ZO-1 genes expression, and increased Blood retinal-barrier (BRB) breakdown, retinal apoptosis and VEGF/VEGFR, as well as VCAM-1/CD45 expressions in the retina compared to normal control group. Niaspan treatment significantly improved clinical and histopathological outcomes; decreased the expressions of VEGF/VEGFR, VCAM-1/CD45, apoptosis and BRB breakdown, significantly increased tight junction proteins and Ang-1/Tie-2 expressions, as well as increased retinal miR-126 expression compared to non-treatment diabetic rats. These data are the first to show that Niaspan treatment ameliorates DR through its repair vascular and inhibits inflammatory effects, and also suggest that the miR-126 pathway may contribute to Niaspan treatment induced benefit effects.

Topics: Angiogenesis Inducing Agents; Angiogenic Proteins; Animals; Apoptosis; Ascorbic Acid; Blood Glucose; Cells, Cultured; Cholecalciferol; Cholesterol; Dehydroepiandrosterone; Delayed-Action Preparations; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Drug Evaluation, Preclinical; Gene Expression; Humans; Hypolipidemic Agents; Male; MicroRNAs; Niacin; Nicotinic Acids; Plant Extracts; Rats, Wistar; Retina; Retinal Vessels; RNA Interference; Tight Junction Proteins; Tight Junctions

The purpose of this investigation is to study the effect of C- taurine complex of antioxidants on blood biochemical parameters in the process of treatment of patients with diabetes mellitus of type II with NPDR. 68 patients (136 eyes) were enrolled in the study. The monitoring of the patient lasted for 3 months. The character of changes of the basic visual functions has been examined. The patients were divided into 2 groups (main and control). Treatment of patients with main group conducted antioxidant complex Taurine + Vitamin C for 42 days. namely. Thus, we have revealed antioxidant activity of the combination of taurine and vitamin C with positive effect on the indexes of carbohydrate, lipid metabolism and hepatoprotective characteristics in patients with diabetes mellitus type II with NPDR. Taking into consideration the peculiarities of correlation relationships between functional, clinical and biochemical parameters and the results of experimental studies on animal it is acceptable to use Taurine complex + Vitamin C as part of conservative treatment of patients with diabetes mellitus type II with NPDR.

Topics: Antioxidants; Ascorbic Acid; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Humans; Lipid Metabolism; Lipids; Taurine

To investigate the ability of an aqueous extract of the leaves of Sansevieria liberica (S. liberica) to alter the hematology, plasma biochemistry and ocular indices of oxidative stress in alloxan-induced diabetic rats.. Diabetes mellitus was induced by injection of alloxan (80 mg/kg body weight), via the tail vein. The extract was administered orally at 100, 200 and 300 mg/kg body weight (both to normal and diabetic rats), and metformin at 50 mg/kg body weight.. Compared to test control, the treatment dose dependently, significantly lowered (P<0.05) ocular malondialdehyde content, atherogenic indices, red cell, total white cell and lymphocyte counts, mean cell hemoglobin concentration; and plasma levels of glucose, triglyceride, total-, very low density lipoprotein-, low density lipoprotein- and non-high density lipoprotein cholesterols, total, conjugated and unconjugated bilirubin, sodium, urea, blood urea nitrogen, as well as plasma activities of alkaline phosphatase, alanine and aspartate transaminases. However, the treatment significantly increased (P<0.05) hematocrit, hemoglobin concentration, mean cell hemoglobin, and mean cell volume, neutrophil and monocyte counts, and plasma levels of high density lipoprotein cholesterol, potassium, chloride, calcium, bicarbonate and total protein, ocular ascorbic acid content and ocular activities of catalase and superoxide dismutase. This study showed the hypoglycemic, hypolipidemic, immune-modulating, ocular-, hepato-renal and cardio-protective potentials of the extract.. All these, support the use of the leaves of S. liberica in African traditional health care practices for the management of diabetes mellitus.

Topics: Animals; Ascorbic Acid; Blood Glucose; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Electrolytes; Eye; Lipids; Malondialdehyde; Oxidative Stress; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Sansevieria

Type 2 Diabetes Mellitus (DM) is increasing worldwide and affects ∼11% of the Hong Kong population. Diabetic retinopathy (DR) is a common cause of vision loss in type 2 DM. Risk of DR is increased by poor glycemic control, elevated lipids, and blood pressure, but it is not possible to predict the development or progression of DR at an individual level. Increased oxidative stress is thought to play a role. The use of a wider biomarker profile incorporating biomarkers of antioxidant status and oxidative stress may aid identification of individuals at higher risk or at very early stages of developing DR.. Four hundred twenty type 2 DM subjects without diabetic complications were investigated. Eyes were examined for DR and anterior and posterior ocular segment pathology. DR was graded according to Early Treatment Diabetic Retinopathy Study criteria. Demographic data were collected. Traditional risk factors plus biomarkers of antioxidant status and oxidative stress in fasting blood and urine were determined.. Overall DR prevalence was 89%. No significant differences in any demographic measures or biomarkers were found among those subjects with different DR grades, or in those without DR. Significant correlations (p < 0.0001) between HbA1c and DNA damage, (ρ = 0.32) and fasting plasma glucose and DNA damage (ρ = 0.52) were seen. DNA damage was also significantly and inversely correlated (p < 0.0001) with both plasma ascorbic acid (ρ = -0.41) and plasma total antioxidant level (ρ = -0.21).. DR prevalence was very high in this group, but no biomarker differences were seen in those with DR compared to those free of DR, or in those with different degrees of severity of DR. This group of 420 subjects is being followed up to investigate whether the extended biomarker profile at baseline is related to progression of and/or incident DR.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Retinopathy; DNA Damage; Fasting; Glycated Hemoglobin; Hong Kong; Humans; Middle Aged; Oxidative Stress; Prevalence; Risk Factors

To explore the metabolic profile of vitreous fluid of patients with proliferative diabetic retinopathy (PDR) using 1H-NMR-based metabonomic analysis.. 1H-NMR spectra were acquired from vitreous samples obtained during vitrectomy from 22 patients with type 1 diabetes with PDR and from 22 nondiabetic patients with macular hole (control group). Data analysis included a principal component analysis and partial least squares discriminant analysis (PLS-DA). In addition, 1H-(1)H and 1H-(13)C HMQC correlation spectra were acquired for the identification of metabolites. Furthermore, the main metabolites accounting for the differences in metabolic profile were assessed by current biochemical methods.. Lactate was the most abundant metabolite, and it was present at higher levels in samples from PDR patients than from nondiabetic patients (P=0.02). Glucose was significantly higher in samples from PDR patients than nondiabetic patients (P=0.03). After removing the lactate peak at 1.35 ppm and with the use of PLS-DA, a model was obtained that was able to correctly classify 19 of 22 patients with PDR and 18 of 22 controls, resulting in a sensitivity of 86% and a specificity of 81%. The main metabolites involved in this specific pattern recognition were galactitol and ascorbic acid (AA); levels of both were significantly lower in PDR patients.. 1H-NMR-based metabonomic analysis of vitreous fluid permits the obtainment of a metabolic signature of PDR. Apart from the higher abundance of lactate and glucose, significant deficits of galactitol and AA are the main metabolic fingerprints of vitreous fluid from PDR patients.

Topics: Adult; Ascorbic Acid; Carbon Isotopes; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Female; Galactitol; Glucose; Humans; Lactic Acid; Least-Squares Analysis; Male; Metabolomics; Middle Aged; Nuclear Magnetic Resonance, Biomolecular; Protons; Vitreous Body

To investigate whether the micronutrients that were shown to reduce the risk of development of age-related macular degeneration in the Age-Related Eye Disease Study (AREDS) can have the same effect on the development of diabetic retinopathy in rats, and to understand the possible mechanisms.. Streptozotocin-induced diabetic rats received a powdered diet with or without supplemental micronutrients (ascorbic acid, vitamin E, beta-carotene, zinc, and copper). The retina was used after the rats had diabetes for 12 months to detect vascular histopathology and to measure the biochemical parameters and messenger RNA levels of the genes involved in oxidative and nitrative stress.. The AREDS-based micronutrients prevented a diabetes-induced increase in the number of retinal acellular capillaries. In the same rats, micronutrients inhibited increases in retinal oxidatively modified DNA and nitrotyrosine and decreases in manganese superoxide dismutase. Diabetes-induced alterations in the messenger RNA expression of mitochondrial electron transport complex III (coenzyme Q cytochrome-c reductase) and inducible nitric oxide synthase were also prevented.. Age-Related Eye Disease Study-based micronutrients inhibit the development of diabetic retinopathy in rodents by inhibiting oxidative and nitrative stress.. Micronutrients that slow down the onset and progression of age-related macular degeneration have the potential to inhibit the development of diabetic retinopathy.

Topics: Animals; Ascorbic Acid; beta Carotene; Body Weight; Copper; Deoxyadenosines; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Diet; Eating; Electron Transport Complex III; Glycated Hemoglobin; Immunoenzyme Techniques; Male; Micronutrients; Nitric Oxide Synthase Type II; Oxidative Stress; Polymerase Chain Reaction; Rats; Rats, Inbred Lew; Retinal Vessels; RNA, Messenger; Superoxide Dismutase; Tyrosine; Vitamin E; Zinc Oxide

We tested the hypothesis that green tea prevents diabetes-related tissue dysfunctions attributable to oxidation. Diabetic rats were treated daily with tap water, vitamins C and E, or fresh Japanese green tea extract. After 12 months, body weights were decreased, whereas glycated lysine in aorta, tendon, and plasma were increased by diabetes (P < 0.001) but unaffected by treatment. Erythrocyte glutathione and plasma hydroperoxides were improved by the vitamins (P < 0.05) and green tea (P < 0.001). Retinal superoxide production, acellular capillaries, and pericyte ghosts were increased by diabetes (P < 0.001) and improved by green tea and the vitamins (P variable). Lens crystallin fluorescence at 370/440 nm was ameliorated by green tea (P < 0.05) but not the vitamins. Marginal effects on nephropathy parameters were noted. However, suppressed renal mitochondrial NADH-linked ADP-dependent and dinitrophenol-dependent respiration and complex III activity were improved by green tea (P variable). Green tea also suppressed the methylglyoxal hydroimidazolone immunostaining of a 28-kDa mitochondrial protein. Surprising, glycoxidation in tendon, aorta, and plasma was either worsened or not significantly improved by the vitamins and green tea. Glucosepane cross-links were increased by diabetes (P < 0.001), and green tea worsened total cross-linking. In conclusion, green tea and antioxidant vitamins improved several diabetes-related cellular dysfunctions but worsened matrix glycoxidation in selected tissues, suggesting that antioxidant treatment tilts the balance from oxidative to carbonyl stress in the extracellular compartment.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Glucose; Body Weight; Camellia sinensis; Collagen; Cross-Linking Reagents; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Diabetic Retinopathy; Feeding Behavior; Glycation End Products, Advanced; In Vitro Techniques; Male; Mitochondria; Oxygen Consumption; Phytotherapy; Rats; Rats, Inbred Lew; Tea; Vitamin E

Non Insulin Dependent Diabetes Mellitus is responsible for 60% cases of retinopathy in the population and is one of the common cause of blindness. Oxidative stress as measured by the levels of malondialdehyde, superoxide dismutase (SOD), glutathione peroxidase (GPx) and vitamin C was measured in 50 normal controls, 40 diabetics without complications, 22 diabetics with proliferative and 20 with nonproliferative retinopathy respectively. Our finding suggests that lipid peroxidation increases (P < 0.001) with the increase in severity and duration of diabetes. Antioxidants SOD and vitamin C decrease with the progression of the disease, however GPx tends to increase in the later part of the disease.

Topics: Adult; Antioxidants; Ascorbic Acid; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Glutathione Peroxidase; Humans; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Superoxide Dismutase

The potential protective effect of vitamins C and E against the development of diabetic retinopathy has not been thoroughly evaluated in epidemiologic studies.. The objective was to study the association between prevalent diabetic retinopathy and intake of vitamins C and E in participants of the Atherosclerosis Risk in Communities Study.. A total of 1353 subjects with type 2 diabetes diagnosed between 1993 and 1995 or before were included. Nutrient intake was assessed with a food-frequency and supplement questionnaire administered between 1987-1989 and 1993-1995. Prevalent retinopathy (n = 224) was determined in 1993-1995 from graded fundus photographs.. No association of retinopathy with intake of vitamin C or E from food alone or from food and supplements combined was observed. The odds ratios and 95% CIs for retinopathy for quartile 4 compared with quartile 1 of vitamins C and E intakes from food and supplements combined were 1.1 (0.7, 1.9) and 1.3 (0.8, 2.2), respectively, after adjustment for diabetes treatment and serum glucose. There was a significant interaction of the observed relations with serum glucose concentration (P < 0.05). Additionally, a decreased odds of retinopathy was found among users (reported use > or =3 y before 1993-1995) of vitamin C or E supplements or multisupplements compared with reported use of no supplements: 0.5 (0.3, 0.8), 0.5 (0.2, 0.8), and 0.4 (0.2, 0.9), respectively.. No significant overall associations were observed between risk of retinopathy and intake of major dietary antioxidants. The observed association between risk of retinopathy and supplement use may reflect nondietary factors or a possible benefit of supplementation.

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Diet; Dietary Supplements; Epidemiologic Studies; Female; Health Surveys; Humans; Male; Middle Aged; Nutrition Surveys; Odds Ratio; Prevalence; Risk Factors; Surveys and Questionnaires; Vitamin E

The protective relation of ascorbic acid and alpha-tocopherol to the development of diabetic retinopathy has not been thoroughly evaluated in epidemiologic studies. The association of prevalent diabetic retinopathy with serum ascorbic acid and alpha-tocopherol was studied among participants with type 2 diabetes (>or=40 years) (n = 998) in the Third National Health and Nutrition Examination Survey (1988-1994); 20% of the sample (n = 199) had prevalent retinopathy. The overall odds ratio for retinopathy among participants in quartile 4 compared with quartile 1 for serum ascorbic acid was 1.3 (95% confidence interval: 0.8, 2.3), with a p for trend = 0.60 after adjustment for the confounders of smoking, race, waist/hip ratio, hypertension, and duration of diabetes. The overall odds ratio for retinopathy among participants in quartile 4 compared with quartile 1 for serum alpha-tocopherol was 2.7 (95% confidence interval: 1.6, 4.6), with a p for trend = 0.14 after adjustment for confounders. After removal of supplement users of vitamin C (n = 307) or vitamin E (n = 298), the odds ratio changed direction or was attenuated: adjusted odds ratios for retinopathy among participants in quartile 4 compared with quartile 1 for serum ascorbic acid and alpha-tocopherol = 0.7 (95% confidence interval: 0.3, 1.4) and 1.6 (95% confidence interval: 0.9, 2.9), respectively. In summary, no significant associations were observed between serum levels of major dietary antioxidants and retinopathy. Recent use of supplements for treatment of complications of diabetes may explain the direct associations.

Topics: Adult; Aged; alpha-Tocopherol; Ascorbic Acid; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Dietary Supplements; Epidemiologic Studies; Female; Health Surveys; Humans; Male; Middle Aged; Nutrition Surveys; Odds Ratio; Prevalence

Oxidative stress is increased in the retina in diabetes, and long-term administration of antioxidants inhibits the development of retinopathy in diabetic rats. The purpose of this study is to determine how diabetes affects the activation of a redox-sensitive nuclear transcriptional factor in the retina, NF-kappaB, and its inhibition by antioxidants. Alloxan diabetic rats were assigned to receive standard diet or the diet supplemented with multiple antioxidants, including ascorbic acid, Trolox, dl alpha-tocopherol acetate, N-acetyl cysteine, beta-carotene, and selenium for up to 14 months. NF-kappaB activation, oxidative stress and nitric oxides were measured in the retina at 2, 8 and 14 months of diabetes. Retinal NF-kappaB was activated by about 60% at two months after induction of diabetes, remained activated for up to 14 months of diabetes, and the duration of diabetes had no effect on the intensity of NF-kappaB activation. Similarly, oxidative stress and nitric oxides were elevated by over 50% in the retina of rats diabetic for 14 months, and nitrotyrosine levels were elevated by over two folds. Administration of the antioxidants to the rats for the entire duration of diabetes inhibited activation of NF-kappaB and elevations in oxidative stress, nitric oxides and nitrotyrosine formation without ameliorating the severity of hyperglycemia. These in vivo results were confirmed by in vitro studies showing that high glucose activates NF-kappaB and elevates NO and lipid peroxides in both retinal endothelial cells and pericytes that can be inhibited by antioxidants. Thus, the results suggest that the activation of retinal NF-KB in diabetes is an early event in the development of retinopathy, and it remains active when the retinal capillary cell death is accelerating, and histopathology is developing. Beneficial effects of antioxidants on the development of diabetic retinopathy might involve inhibition of NF-kappaB activation and its downstream pathways in the retina.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Chromans; Cysteine; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Glucose; Lipid Peroxides; Male; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Rats; Rats, Sprague-Dawley; Retina; Selenium; Tyrosine

Vitamin C exists in two major forms. The charged form, ascorbic acid (AA), is taken up into cells via sodium-dependent facilitated transport. The uncharged form, dehydroascorbate (DHA), enters cells via glucose transporters (GLUT) and is then converted back to AA within these cells. Cell types such as certain endothelial and epithelial cells as well as neurons that are particularly prone to damage during diabetes tend to be those that appear to be dependent on GLUT transport of DHA rather than sodium-dependent AA uptake. We hypothesize that diabetic neuropathies, nephropathies and retinopathies develop in part by exclusion of DHA uptake by GLUT transporters when blood glucose levels rise above normal. AA plays a central role in the antioxidant defense system. Exclusion of DHA from cells by hyperglycemia would deprive the cells of the central antioxidant, worsening the hyperglycemia-induced oxidative stress level. Moreover, AA participates in many cellular oxidation-reduction reactions including hydroxylation of polypeptide lysine and proline residues and dopamine that are required for collagen production and metabolism and storage of catecholamines in neurons. Increase in the oxidative stress level and metabolic perturbations can be expected in any tissue or cell type that relies exclusively or mainly on GLUT for co-transport of glucose and DHA including neurons, epithelial cells, and vascular tissues. On the other hand, since DHA represents a significant proportion of total serum ascorbate, by increasing total plasma ascorbate concentrations during hyperglycemia, it should be possible to correct the increase in the oxidative stress level and metabolic perturbations, thereby sparing diabetic patients many of their complications.

Topics: Ascorbic Acid; Biological Transport; Blood Glucose; Dehydroascorbic Acid; Diabetes Mellitus; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Endothelium; Humans; Kidney; Models, Biological; Monosaccharide Transport Proteins; Nervous System; Oxidative Stress; Retina

Apoptosis of retinal endothelial cells and pericytes is postulated to contribute to the development of retinopathy in diabetes. The goal of this study is to investigate diabetes-induced activation of retinal caspase-3, an apoptosis executer enzyme, in retina, and examine the effects of antioxidants on the activation. Caspase-3 activation was determined in the retina of alloxan diabetic rats (2-14 months duration) and in the isolated retinal capillary cells (endothelial cells and pericytes) by measuring cleavage of caspase-3 specific fluorescent substrate, and cleavage of caspase-3 holoenzyme and poly (ADP ribosyl) polymerase. Effect of antioxidants on the activation of caspase-3 was determined by feeding a group of diabetic rats diet supplemented with a comprehensive mixture of antioxidants, including Trolox, alpha-tocopherol, N-acetyl cysteine, ascorbic acid, beta-carotene and selenium for 2-14 months, and also under in vitro conditions by incubating isolated retinal capillary cells with antioxidants with wide range of actions. Caspase-3 was activated in the rat retina at 14 months of diabetes (P < 0.05 vs. normal), but not at 2 months of diabetes, and administration of antioxidants for the entire duration inhibited this activation. In the isolated retinal capillary cells incubated in 25 mM glucose medium, caspase-3 activity was increased by 50% compared to the cells incubated in 5 mM glucose (P < 0.02), and antioxidants or caspase-3 inhibitor inhibited this increase. Our results suggest that increased oxidative stress in diabetes is involved in the activation of retinal caspase-3 and apoptosis of endothelial cells and pericytes. Antioxidants might be inhibiting the development of diabetic retinopathy by inhibiting microvascular apoptosis.

Topics: Acetylcysteine; alpha-Tocopherol; Animals; Antioxidants; Apoptosis; Ascorbic Acid; beta Carotene; Caspase 3; Caspases; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Endothelium, Vascular; Enzyme Activation; Glucose; In Vitro Techniques; Male; Oxidative Stress; Pericytes; Poly(ADP-ribose) Polymerases; Rats; Rats, Sprague-Dawley; Retina; Selenium; Thiobarbituric Acid Reactive Substances

Loss of retinal pericytes is the initial deficit in the early stage of diabetic retinopathy. Glycated albumin (GA) forms under hyperglycemic conditions and exists in the retinal blood vessels of diabetic patients with retinopathy. In this study, using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) reduction test, we investigated whether GA induces cytotoxicity in cultured bovine retinal pericytes, and whether the antioxidants, l-ascorbic acid, Trolox, and probucol, provide any protection from GA-mediated cytotoxicity. GA induced pericyte death in a dose-dependent manner. With increasing time, GA-induced cytotoxicity also increased despite no strict time dependence. Furthermore, this cell death was found to be mediated both by apoptosis, which was confirmed by apoptosis-specific fluorescent staining of nuclei and cell membranes, and mitochondrial damage, as elucidated by electron microscopy. All three antioxidants used in this study partially protected against GA-induced pericyte death, suggesting that oxidative stress plays a role in GA-induced pericyte death. The results indicate that GA induces cell death in cultured bovine retinal pericytes, and that certain antioxidants may reduce this cytotoxicity.

Topics: Animals; Antioxidants; Ascorbic Acid; Cattle; Cell Death; Cell Survival; Cells, Cultured; Chromans; Cytoprotection; Diabetic Retinopathy; Dose-Response Relationship, Drug; Glycated Serum Albumin; Glycation End Products, Advanced; Mitochondria; Oxidative Stress; Pericytes; Probucol; Retina; Retinal Vessels; Serum Albumin; Tetrazolium Salts; Thiazoles; Time Factors

Antioxidants were administered to diabetic rats and experimentally galactosemic rats to evaluate the ability of these agents to inhibit the development of diabetic retinopathy. Alloxan diabetic rats and nondiabetic rats that were fed 30% galactose randomly received standard diets or the diets supplemented with ascorbic acid and alpha-tocopherol (vitamins C+E diet) or a more comprehensive mixture of antioxidants (multi-antioxidant diet), including Trolox, alpha-tocopherol, N-acetyl cysteine, ascorbic acid, beta-carotene, and selenium. Diabetes or galactose feeding of at least 12 months resulted in pericyte loss, acellular capillaries, and basement membrane thickening. Compared with diabetic controls, the development of acellular capillaries was inhibited by 50% (P < 0.05) in diabetic rats that received supplemental vitamins C+E, and the number of pericyte ghosts tended to be reduced. The vitamins C+E supplement had no beneficial effect in galactosemic rats, but these rats consumed only approximately half as much of the antioxidants as the diabetic rats. The multi-antioxidant diet significantly inhibited ( approximately 55-65%) formation of both pericyte ghosts and acellular capillaries in diabetic rats and galactosemic rats (P < 0.05 vs. controls), without affecting the severity of hyperglycemia. Parameters of retinal oxidative stress, protein kinase C activity, and nitric oxides remained elevated for at least 1 year of hyperglycemia, and these abnormalities were normalized by multi-antioxidant therapy. Thus, long-term administration of antioxidants can inhibit the development of the early stages of diabetic retinopathy, and the mechanism by which this action occurs warrants further investigation. Supplementation with antioxidants can offer an achievable and inexpensive adjunct therapy to help inhibit the development of retinopathy in diabetes.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Chromans; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Diet; Dietary Supplements; Galactosemias; Male; Pericytes; Rats; Rats, Sprague-Dawley; Retina; Retinal Diseases; Selenium; Vitamin E

To investigate the role of oxidative stress in the development of diabetic retinopathy.. This study included 25 patients with diabetic retinopathy (group I), 34 patients with non-insulin-dependent diabetes mellitus without any angiopathy complications (group II) and 26 healthy subjects (group III). The serum malondialdehyde (MDA)-like metabolite levels as an index of lipid peroxidation, the erythrocyte glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and serum vitamin C levels of the patients and healthy subjects were measured.. The mean serum concentration of MDA-like metabolites of patients in group I was 4.38 +/- 1.31 nmol/ml, in group II was 3.38 +/- 0.95 nmol/ml and in group III was 2.61 +/- 0.85 nmol/ml. There were significant differences between the groups (p = 0.001 for group I compared with group II, p = 0.0001 for group I compared with group III and p = 0.002 for group II compared with group III). There was a significant correlation between the serum lipid peroxidation concentrations and duration of the disease (r = 0.36, p = 0.047). The mean erythrocyte GSH-Px and SOD levels of group I were respectively 68.97 +/- 18.04 and 1597.78 +/- 296.46 U/g Hb, of group II were 64.30 +/- 19.26 and 1581.33 +/- 278.08 U/g Hb, and of group III were 65.52 +/- 17.58 and 1587.44 +/- 281.17 U/g Hb. There were no significant differences among the antioxidant enzyme levels in the three groups (p > 0.05). The mean serum vitamin C level in group I was 42.72 +/- 8.90 mumol/l, in group II was 49.26 +/- 11.52 mumol/l and in group III was 58.57 +/- 9.75 mumol/l. There were significant differences among the mean serum vitamin C levels of the three groups (p = 0.02 for group I versus group II p = 0.001 for group I versus group III and p = 0.002 for group II versus group III).. Free radicals forming in diabetes mellitus and increasing over time may play a role in the development of diabetic retinopathy, which is an important complication of the disease.

Topics: Adult; Aged; Ascorbic Acid; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Erythrocytes; Female; Glutathione Peroxidase; Humans; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Superoxide Dismutase

Diabetic retinopathy (DR) is a major cause of visual impairment and blindness in adults. Antioxidant nutrients, such as vitamins C and E and beta-carotene, may be protective of some eye disorders, such as cataract and age-related macular degeneration, but a relationship between these nutrients and DR has yet to be defined. The purpose of this study was to examine the relation between dietary and supplement intakes of vitamins C, E, and beta-carotene and the risk of DR.. Both cross-sectional and longitudinal data were collected from participants in the San Luis Valley Diabetes Study, including non-Hispanic white and Hispanic adults in southern Colorado.. A total of 387 participants with type 2 diabetes completed at least 1 complete retinal examination and 24-hour dietary recall (including vitamin supplement use).. Type 2 diabetes was defined according to World Health Organization criteria. DR was assessed by retinal photographs, using the Airlie House criteria to classify DR as none, background, preproliferative, or proliferative. Data for both eyes, from up to three clinic visits per participant, were used for analysis. Ordinal logistic regression analysis was used, taking advantage of multiple clinic visits by individual participants and observations from both eyes, to assess the risk for increased DR severity over time as a function of changes in intake of vitamin C, vitamin E, and beta-carotene. Six categories of intake for each nutrient (first to fourth quintiles and ninth and tenth deciles) were considered to ascertain any potential threshold effect. Analyses accounted for age, duration of diabetes, insulin use, ethnicity, glycated hemoglobin, hypertension, gender, and caloric intake.. An increase over time in vitamin C intake from the first to ninth deciles was associated with a risk for increased severity of DR (odds ratio = 2.21, P = 0.01), although excess risk was not observed for the tenth decile or the second through fourth quintiles compared to the first quintile. Increased intake of vitamin E was associated with increased severity of DR among those not taking insulin (odds ratios = 2.69, 2.59, 3.33, 5.65, 3.79; P < 0.02, for an increase over time from the first to the second through fourth quintiles and ninth and tenth deciles, respectively). Among those taking insulin, increased intake of beta-carotene was associated with a risk for severity of DR (odds ratio = 3.31, P = 0.003, and 2.99, P = 0.002, respectively, for the ninth and tenth deciles compared to the first quintile).. No protective effect was observed between antioxidant nutrients and DR. Depending on insulin use, there appeared to be a potential for deleterious effects of nutrient antioxidants. Further research is needed to confirm associations of nutrient antioxidant intake and DR.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; California; Colorado; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Dietary Supplements; Female; Humans; Insulin; Longitudinal Studies; Male; Middle Aged; Prevalence; Risk Factors; 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

Reactive oxygen species are thought to be implicated in the pathogenesis of various human diseases. They are generated endogenously under physiological and pathological conditions but also upon exposure to exogenous challenge. The organism maintains defense systems against reactive oxygen species, including enzymes and low-molecular-weight antioxidants. Important antioxidants such as vitamins E and C and carotenoids are provided from the diet. Vitamin E, as the major chain-breaking antioxidant, inhibits lipid peroxidation, thus preventing membrane damage and modification of low-density lipoproteins. It is regenerated by the water-soluble vitamin C. Carotenoids efficiently scavenge singlet molecular oxygen and peroxyl radicals. There is increasing evidence from epidemiological studies, animal experiments, and in vitro investigations that an increased intake of antioxidants is associated with a diminished risk for several diseases.

Topics: Animals; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Diabetic Nephropathies; Diabetic Retinopathy; Diet; Humans; Reactive Oxygen Species; Vitamin E

The role of oxidant stress in the causation of chronic tissue damage is being increasingly recognized. Oxidant stress is usually countered by abundant supply of antioxidants. If concomitant antioxidant deficiency occurs, oxidant stress may produce tissue damage. We took up a study on antioxidant status in non-insulin dependent diabetes mellitus (NIDDM) patients with and without retinopathy and compared them with a control non-diabetic group. The levels of superoxide dismutase (SOD) were significantly reduced in all diabetic patients, i.e., those with and without retinopathy. However, the lowest levels were found in the diabetic patients with retinopathy. Vitamin E and vitamin C levels were also markedly lower in the diabetic patients. There was a paradoxical rise in the catalase and glutathione peroxidase (GPx) in the diabetic patients with retinopathy. This may be a compensatory mechanism by the body to prevent tissue damage by increasing the levels of the two alternative antioxidant enzymes.

Topics: Adult; Ascorbic Acid; Catalase; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Glutathione Peroxidase; Humans; Male; Middle Aged; Oxidative Stress; Superoxide Dismutase; Vitamin A; Vitamin E

Levels of the intracellular antioxidant, glutathione, become subnormal in retina in diabetes or experimental galactosemia. In order to investigate the cause and significance of this abnormality, activity of gamma-glutamyl transpeptidase (an enzyme important in the synthesis and degradation of glutathione) and levels of reduced glutathione have been measured in retinas of diabetic rats and dogs and of experimentally galactosemic rats and dogs. Retinal gamma-glutamyl transpeptidase activity and glutathione level were significantly less than normal after 2 months of diabetes or galactosemia. In contrast, cerebral cortex from the same diabetic rats and galactosemic rats showed no significant reduction in either gamma-glutamyl transpeptidase activity or glutathione level. These different responses of the two tissues to hyperglycemia might help account for the difference in microvascular disease in these two tissues in diabetes. Consumption of the antioxidants, ascorbic acid (1.0%) plus alpha-tocopherol (0.1%), by diabetic rats and galactosemic rats inhibited the decrease of gamma-glutamyl transpeptidase activity and glutathione levels in retina, suggesting that defects in glutathione regulation in the retina are secondary to hyperglycemia-induced 'oxidative stress'.

Topics: Animals; Antioxidants; Ascorbic Acid; Cerebral Cortex; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Dogs; Drug Therapy, Combination; Galactosemias; gamma-Glutamyltransferase; Glutathione; Rats; Rats, Sprague-Dawley; Retina; Vitamin E

Abnormalities of retinal pericytes and endothelial cells are prominent features of diabetic retinopathy. In this study, we used cultures of bovine retinal cells to examine the regulation of cell-associated proteoglycans, a class of highly sulfated macromolecules important in the regulation of cell growth. Bovine retinal pericytes and endothelial cells were radiolabeled with 35SO4 and cell-associated proteoglycans were removed from the cell surface, quantified, and characterized. The effects of high glucose concentration (25 mM), phorbol 12,13-dibutyrate (PDBu, 0.1 microM), and ascorbic acid (0.1 mM) on cell-associated proteoglycans and growth of these cells were studied. Our results showed that both the ionically bound and the membrane-intercalated forms of cell-associated proteoglycans are present on retinal cells. The predominant cell-associated proteoglycan of pericytes is chondroitin sulfate and for endothelial cells it is heparan sulfate. High glucose concentration and ascorbic acid increased the cell-associated proteoglycans on pericytes but reduced them on endothelial cells. In contrast to this divergent trend, high glucose concentration and ascorbic acid inhibited the growth of both pericytes and endothelial cells. The effects of high glucose on retinal cell-associated proteoglycans were mimicked by PDBu added in a manner to stimulate protein kinase C activity. We conclude that cell-associated proteoglycans are present on retinal pericytes and endothelial cells. High glucose concentration and ascorbic acid affect cell-associated proteoglycans of these two cell types in opposite directions, whereas both suppress the growth of the two cell types. Therefore, it is not likely that high glucose concentration and ascorbic acid change the rate of retinal cell growth directly by affecting cell-associated proteoglycan levels.

Topics: Animals; Ascorbic Acid; Cattle; Cells, Cultured; Diabetic Retinopathy; Endothelium, Vascular; Evaluation Studies as Topic; Glucose; Proteoglycans; Retina

Metabolism of ascorbic acid is deranged in Diabetes Mellitus (DM). One important reason of this derangement is its increased turnover in the process of handling an increased load of free radicals. Anoxia, the triggering factor in the pathogenesis of diabetic retinopathy generates free radicals in anoxia-reperfusion sequence. Any process like argon laser photocoagulation that destroys the anoxic sites and improves oxygenation in retina might hinder the process of generation of free radicals and thus expected to preserve ascorbic acid. In this study plasma total ascorbic acid concentration in matched groups of (I) diabetics with retinopathy with no history of photocoagulation (II) diabetics with retinopathy treated by laser and (III) diabetics without microvascular pathology were measured by 2-4 dinitrophenyl hydrazine method. Plasma total ascorbate concentration was significantly higher in group-II (0.47 +/- 0.09 mg/dl; X +/- SD) in comparison to group-I (0.19 +/- 0.07 mg/dl P < 0.001). The concentration was not significant between group-II and group-III (0.49 +/- 0.06 mg/dl; P = 0.40). Other clinical and metabolic parameters were not significantly different in between the groups. This observation leads to speculation that photocoagulation saves ascorbic acid from excessive turnover in anoxic retina in the process of handling free radicals.

Topics: Ascorbic Acid; Diabetic Retinopathy; Female; Humans; Laser Coagulation; Male; Middle Aged

Diabetics, who developed retinopathy within one year of detection of disease were found to have a significantly low plasma total ascorbate concentration compared to those who developed retinopathy 7-17 years after detection of DM. Traditional metabolic parameters did not show significant difference between the two groups. Thus a severe ascorbate deficiency may be an important determinant in the pathogenesis of retinopathy independent of metabolic status and duration of DM. It merits early supplementation of ascorbic acid to retard the progression of microvascular complication.

Topics: Adult; Ascorbic Acid; Diabetic Retinopathy; Female; Humans; Male; Middle Aged

Abnormalities of both free radical activity and ascorbic acid metabolism have been documented in diabetes, but their biological basis is unclear and their relationship unstudied in any detail. This study was designed to compare changes in antioxidant status and free radical reactions in a group of elderly diabetic patients (with and without retinopathy) with those in a group of age-matched control subjects. No significant differences in thiobarbituric acid (TBA) reactivity, red cell glutathione (GSH) concentrations or diene conjugates (DC) between patients and controls were seen despite significant depletion of ascorbic acid in patients with diabetes, especially in those with retinopathy. The results emphasise the present-day difficulties of measuring free radical activity and demonstrate a marked abnormality in ascorbic acid metabolism in diabetes.

Topics: Aged; Ascorbic Acid; Cholesterol; Dehydroascorbic Acid; Diabetic Retinopathy; Free Radicals; Humans; Middle Aged; Triglycerides

Abnormalities of ascorbic acid metabolism have been reported in experimentally-induced diabetes and in diabetic patients. Ascorbate is a powerful antioxidant, a cofactor in collagen biosynthesis, and affects platelet activation, prostaglandin synthesis and the polyol pathway. This suggests a possible close interrelationship between ascorbic acid metabolism and pathways known to be influenced by diabetes. We determined serum ascorbic acid and its metabolite, dehydroascorbic acid, as indices of antioxidant status, and the ratio, dehydroascorbate/ascorbate, as an index of oxidative stress, in 20 matched diabetic patients with and 20 without microangiopathy and in 22 age-matched control subjects. Each study subject then took ascorbic acid, 1 g daily orally, for six weeks with repeat measurements taken at three and six weeks. At baseline, patients with microangiopathy had lower ascorbic acid concentrations than those without microangiopathy and control subjects (42.1 +/- 19.3 vs 55.6 +/- 20.0, p less than 0.01, vs 82.9 +/- 30.9 mumol/l, p less than 0.001) and elevated dehydroascorbate/ascorbate ratios (0.87 +/- 0.46 vs 0.61 +/- 0.26, p less than 0.01, vs 0.38 +/- 0.14, p less than 0.001). At three weeks, ascorbate concentrations rose in all groups (p less than 0.0001) and was maintained in control subjects (151.5 +/- 56.3 mumol/l), but fell in both diabetic groups by six weeks (p less than 0.01). Dehydroascorbate/ascorbate ratios fell in all groups at three weeks (p less than 0.0001) but rose again in the diabetic groups by six weeks (p less than 0.001) and was unchanged in the control subjects. Dehydroascorbate concentrations rose significantly from baseline in all groups by six weeks of ascorbic acid supplementation (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Aged; Ascorbic Acid; Blood Glucose; Dehydroascorbic Acid; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Female; Fructosamine; Hexosamines; Humans; Male; Reference Values

Plasma total ascorbate status measured by 2.4 dinitrophenyl hydrazine method showed that diabetics (N = 100) had significantly lower plasma total ascorbate compared with 45 age and sex matched non-diabetic controls; 0.34 +/- 0.16 mg/dl vs 0.68 +/- .06 mg/dl, P less than 0.001) regardless of presence or absence of retinopathy and irrespective of mode of treatment. The finding unique to this study was that plasma total ascorbate status in diabetics with retinopathy (0.19 +/- 0.07 mg/dl) was significantly lower than that of uncomplicated diabetics (0.49 +/- 0.06 mg/dl; P less than 0.001). Plasma Glucose had no correlation with plasma ascorbate levels and effect of duration of Diabetes Mellitus (DM) on ascorbate status in diabetics was ambiguous. Diabetics had abnormally fragile cutaneous capillaries detected by Hess test. The incidence of capillary fragility was more in patients with retinopathy. Hess test can be used as an easy and non-invasive test to assess plasma ascorbate status to detect microvascular involvement in DM. The experience of this study reflects that the two distinct microvascular lesions in diabetes, i.e. abnormal dermal capillary fragility and retinopathy may have a common link to ascorbic acid deficiency. An early switching on of the supplementation of ascorbic acid may retard the development of microvascular complications in diabetes.

Topics: Adult; Ascorbic Acid; Blood Glucose; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Retinopathy; Humans; Middle Aged

Recent evidence has suggested that diabetic microangiopathy is associated with increased free radical induced oxidative damage. Ascorbic acid (AA) is a free radical scavenger and using a specific HPLC method we have investigated its concentration and that of its oxidized metabolite dehydroascorbic acid (DHAA) in diabetic patients and matched normal controls. The findings have been related to the presence of microangiopathy and to glycaemic control. Ascorbic acid levels were significantly lower in diabetics (mean +/- SD 42.5 +/- 26.2 mumol/l) compared with controls (58 +/- 21 mumol/l p less than 0.02). Although there was no differences in DHAA levels between the groups the ratio DHAA/AA was increased in diabetics (0.72 +/- 0.8) compared with controls (0.4 +/- 0.2 p less than 0.05). There were no significant differences between insulin and non-insulin dependent patients in these measurements and there was no association with the presence of microangiopathy or poor glycaemic control. The plasma ratio DHAA/AA may be a reflection of increased oxidative stress and our results suggest that diabetics may be less able to prevent oxidative damage occurring due to their lower AA concentrations.

Topics: Ascorbic Acid; Dehydroascorbic Acid; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Fructosamine; Hexosamines; Humans; Middle Aged; Reference Values

Topics: Ascorbic Acid; Aspirin; Calcium Dobesilate; Diabetic Angiopathies; Diabetic Retinopathy; Dipyridamole; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Humans; Pentoxifylline; Platelet Aggregation; Rutin; Thrombelastography; Vision, Ocular

Topics: Animals; Ascorbic Acid; Cells, Cultured; Diabetic Retinopathy; Iron; Lipid Peroxides; Liver; Male; Membrane Lipids; NAD; NADP; Rats; Rats, Inbred Strains; Retina

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