beta-carotene and Retinal-Diseases

Pharmacotherapy with visual cycle modulators (VCMs) is under investigation for retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), Stargardt macular dystrophy (SMD) and nonexudative age-related macular degeneration (AMD), all blinding diseases that lack effective treatment options.. The authors review investigational VCMs, including oral retinoids, 9-cis-retinyl-acetate (zuretinol) and 9-cis-β-carotene, which restore 11-cis-retinal levels in RP and LCA caused by LRAT and RPE65 gene mutations, and may improve visual acuity and visual fields. Therapies for SMD aiming to decrease accumulation of toxic Vitamin A dimers and lipofuscin in the retina and retinal pigment epithelium (RPE) include C20-D3-vitamin A (ALK-001), isotretinoin, VM200, emixustat, and A1120. Mouse models of SMD show promising data for these treatments, though proof of efficacy in humans is currently lacking. Fenretinide and emixustat are investigational VCMs for dry AMD, though neither has been shown to reduce geographic atrophy or improve vision in human trials. A1120 prevents retinol transport into the RPE and may spare the side effects typically seen in VCMs (nyctalopia and chromatopsia) per mouse studies.. Oral VCMs may be feasible treatment options for degenerative retinal diseases based on pre-clinical and some early clinical studies. Further trials are warranted to assess their efficacy and safety in humans.

Topics: Acyltransferases; ATP-Binding Cassette Transporters; beta Carotene; cis-trans-Isomerases; Diterpenes; Humans; Isotretinoin; Phenyl Ethers; Propanolamines; Retinal Diseases; Retinoids; Retinyl Esters; Vitamin A

To examine if long-term supplementation with alpha-tocopherol (AT) or beta-carotene (BC) was associated with the prevalence of vascular changes in retinal arterioles.. An end-of-trial subsample from a double-blind, placebo-controlled clinical trial designed to study the effects of alpha-tocopherol and beta-carotene on lung cancer incidence (ATBC Study).. Source population of Helsinki and the surrounding province.. 1072 men 50-69 years old and smoking at least 5 cigarettes per day at study entry.. Random allocation to one of four supplementation regimens: 50 mg per day alpha-tocopherol, 20 mg per day beta-carotene, both alpha-tocopherol and beta-carotene, or placebo. Median follow-up time was 6.6 years (range 5.2-8.0 years).. Presence of vascular changes in retinal arterioles as determined from end-of-trial retinal color photographs.. Retinal vascular changes were most prevalent in the AT (161 men, 62%), and in the BC (163 men, 62%) groups. The prevalence rate was lowest in the AT plus BC group (161 men, 55%), and slightly higher in the placebo group (145 men, 57%). There was no statistically significant association of either AT (OR 0.9, 95% CI 0.7-1.2) or BC (OR 1.0, 95% CI 0.8-1.3) supplementation with the prevalence of retinal vascular changes after adjusting for major risk factors.. Supplementation with alpha-tocopherol or beta-carotene for a median of 6.6 years does not protect against retinal vascular changes among smoking males.

Topics: Aged; Aged, 80 and over; Antioxidants; Arterioles; Arteriosclerosis; beta Carotene; Double-Blind Method; Finland; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Prevalence; Retinal Artery; Retinal Diseases; Smoking; Vitamin E

Animal research and observational studies in man suggest a protective effect of antioxidant vitamins in the development of age-related maculopathy (ARM).. The ATBC study, a population-based, controlled clinical trial of alpha-tocopherol and beta carotene to prevent lung cancer, took place in Finland between 1984 and 1993. Over 29,000 smoking males aged 50 to 69 years were randomly assigned to alpha-tocopherol (AT; 50 mg/day), beta-carotene (BC; 20 mg/day), both of these, or placebo. We performed an end-of-trial ophthalmological examination on a random sample of 941 participants aged 65 years or more from two of the fourteen study areas, to discover if the five to eight-year intervention with alpha-tocopherol and/or beta-carotene had been associated with a difference in ARM prevalence. Age-related maculopathy was assessed using colour photographs of the macula.. Altogether, 269 cases of ARM were found; there were more cases in the AT group (32%; 75/237), BC group (29%; 68/234), and combined antioxidant group (28%; 73/257) than in the placebo group (25%; 53/213). However, neither substance was significantly associated with the risk of ARM in a logistic regression analysis controlling for possible risk factors.. No beneficial effect of long-term supplementation with alpha-tocopherol or beta-carotene on the occurrence of ARM was detected among smoking males.

Topics: Aged; Aging; Antioxidants; beta Carotene; Double-Blind Method; Finland; Humans; Lung Neoplasms; Macula Lutea; Male; Prevalence; Retinal Diseases; Vitamin E

Diabetic retinopathy (DR) is one of the leading causes of blindness. Carotenoids are plant-derived pigments required for general health and particularly for vision. In this study, we evaluated the dietary intake and blood carotenoid levels of type 2 diabetes (T2D) patients with and without DR. A cross-sectional case-control study was conducted among 151 age-matched controls and 344 T2D patients, of which 194 had DR and 150 had no DR (NDR). After a complete ophthalmic examination, the demographic, anthropometric and clinical profiles were obtained. Carotenoids in the plasma were measured by HPLC and dietary intakes were obtained using a food frequency questionnaire. The mean plasma levels of carotenoids (except γ-carotene) were significantly lower in the DR group compared to the Control and NDR groups. The dietary intakes of zeaxanthin, lycopene, α-carotene and β-carotene were significantly lower in the NDR group compared to the Control group, and were further lower in the DR group compared to the NDR group. Plasma carotenoid levels were significantly inversely associated with the duration of diabetes, RBS and HbA1c but positively associated with HDL. This study demonstrated decreased plasma levels and lower dietary intakes of carotenoids in DR subjects.

Topics: beta Carotene; Carotenoids; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Eating; Female; Glycated Hemoglobin; Humans; Lycopene; Male; Middle Aged; Pilot Projects; Retinal Diseases; Surveys and Questionnaires; Zeaxanthins

The retinoid cycle enzymes regenerate the visual chromophore 11-cis retinal to enable vision. Mutations in the genes encoding the proteins of the retinoid cycle are the leading cause for recessively inherited retinal dystrophies such as retinitis pigmentosa, Leber congenital amaurosis, congenital cone-rod dystrophy and fundus albipunctatus. Currently there is no treatment for these blinding diseases. In previous studies we demonstrated that oral treatment with the 9-cis-β-carotene rich Dunaliella Bardawil algae powder significantly improved visual and retinal functions in patients with retinitis pigmentosa and fundus albipunctatus. Here we developed a convenient and economical synthetic route for biologically active 9-cis-β-carotene from inexpensive building materials and demonstrated that the molecule is stable for at least one month. Synthetic 9-cis-β-carotene rescued cone photoreceptors from degeneration in eye cup cultures of mice with a retinoid cycle genetic defect. This study suggests that synthetic 9-cis-β-carotene may serve as an effective treatment for retinal dystrophies involving the retinoid cycle.

Topics: Animals; beta Carotene; Cells, Cultured; Chemistry Techniques, Synthetic; Disease Models, Animal; Mice; Photoreceptor Cells, Vertebrate; Provitamins; Retinal Degeneration; Retinal Diseases; Retinitis Pigmentosa

The purpose of these studies was to evaluate the effects of light damage on Japanese quail whose retinal carotenoids had been experimentally manipulated through altered diets. The birds were raised 6 months on a commercial turkey diet (T), on a custom carotenoid-deficient diet (C-) containing 90% less carotenoid than the T diet, or on Z+ diet [the C- diet supplemented with natural zeaxanthin (35mgkg(-1) food)]. Equal numbers of males and females on each diet were exposed to nine intervals (1hr on, 2hr off) of 3200lux cool white light, then placed in the dark for 14hr before tissue collection. One retina was immediately frozen for HPLC analysis; the other eye was immediately fixed and processed for microscopy. There were no significant differences in the retinal carotenoid concentrations in hatch-mates that were and were not exposed to light. Supplementation resulted in three- to four-fold increases in retinal zeaxanthin and no change in retinal lutein or alpha-tocopherol, but the C- diet did not reduce the retinal carotenoid concentration in C- birds below that in T birds. The light-exposed retinas had significant numbers of apoptotic photoreceptors and photoreceptor ghosts. The number of ghosts was negatively correlated with the number of dying photoreceptors (P<0.05), and with retinal concentrations of zeaxanthin, alpha-tocopherol or gamma-tocopherol (P<0.04, 0.02, 0.04, respectively), but not with lutein. The number of dying photoreceptors was positively correlated with alpha-tocopherol and the sum alpha-tocopherol plus zeaxanthin (P<0.1; P0.04). Photoreceptor death was semi-quantitatively scored, assuming that ghosts were formed by removal of apoptotic photoreceptors with nuclear condensation. Stepwise regression produced a good model (r(2)=0.67;P <0.0001) for predicting death scores from retinal concentrations of zeaxanthin (Standard Coefficient=-0.76) and lutein (Standard Coefficients=+0.43). Absence of lutein in gender-specific analyses suggests lutein served as surrogate marker for gender. Combined analysis of the C- and T birds also demonstrated that dying photoreceptors were negatively correlated with retinal zeaxanthin. These data confirm our previous report that retinal carotenoids prevent photoreceptor cell death, and provide the first direct evidence that retinal zeaxanthin protects photoreceptors from light-induced death.

Topics: Age Factors; Animals; Apoptosis; beta Carotene; Carotenoids; Coturnix; Dietary Supplements; Female; Light; Lutein; Macula Lutea; Male; Photoreceptor Cells, Vertebrate; Retinal Diseases; Time Factors; Tocopherols; Xanthophylls; Zeaxanthins

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

Continuous illumination of 18,175 lx caused degeneration of the retinal photoreceptor cells in albino rats, accompanied by increase of malondialdehyde (MDA) 3 days after the light exposure. The MDA decreased gradually to return to normal 8 days after the exposure. Administration of vitamin E or beta-carotine both prevented the increase of retinal lipid peroxide with amelioration of the photic injury to the retinal structures, though the effects were closely related to the dosage and time of medication.

Topics: Animals; Antioxidants; beta Carotene; Carotenoids; Lipid Peroxidation; Photic Stimulation; Photoreceptor Cells; Rats; Rats, Wistar; Retinal Diseases; Vitamin E

A matched-control study of plasma retinol, alpha-tocopherol, carotenoid, and cholesterol concentrations and the polyunsaturated fatty acid content of plasma and erythrocyte phospholipids was undertaken in 65 elderly patients with age-related maculopathy and 65 control subjects matched for age and sex. Despite the high statistical power of the study and large variations between subjects in the variables under consideration, no significant differences were noted between patients and control subjects. However, several statistically significant differences were noted between male and female subjects independent of their classification with maculopathy or as controls and age: plasma cholesterol, total phospholipids, alpha-tocopherol, and beta-cryptoxanthin concentrations were higher in females than in males. The mean plasma cholesterol concentration for the upper tertile of the whole sample was 7.6 mmol/L. Plasma concentrations of total carotenoids, alpha-carotene, and beta-carotene, but not alpha-tocopherol, were significantly lower in smokers than in non-smokers. The results of this study do not provide any evidence in favor of changing the dietary intake of polyunsaturated fatty acids or fat-soluble vitamins to protect against age-related maculopathy.

Topics: Aged; Aging; beta Carotene; Carotenoids; Cholesterol; Cryptoxanthins; Fatty Acids, Essential; Female; Humans; Macula Lutea; Male; Phospholipids; Retinal Diseases; Sex Characteristics; Smoking; Solubility; Vitamin E; Vitamins; Xanthophylls

As reported earlier, crystalline yellow-glistening deposits in the retinal inner layer were identified in 22 of 53 patients treated with PHENORO (containing 10 mg beta-carotene and 15 mg canthaxanthin per capsule) for various light sensitive dermatoses at cumulative doses of canthaxanthin of up to 178 g for up to 12 years. 14 of the 22 patients with deposits could now be investigated again, 5 years after discontinuation of treatment. There was an extensive reduction of the number of deposits, confirming other reports which have demonstrated that the formation of the crystalline deposits is reversible. Analysis of serum samples revealed significant concentrations of canthaxanthin, resulting from the intake of this carotenoid via food.

Topics: Adult; Aged; beta Carotene; Canthaxanthin; Carotenoids; Crystallization; Dose-Response Relationship, Drug; Drug Combinations; Female; Fundus Oculi; Humans; Liver Function Tests; Male; Middle Aged; Photosensitivity Disorders; Prevalence; Retina; Retinal Diseases; Visual Acuity

Topics: beta Carotene; Canthaxanthin; Carotenoids; Crystallization; Drug Combinations; Female; Humans; Long-Term Care; Macula Lutea; Retinal Diseases

Twenty-five patients (erythropoietic protoporphyria 23, polymorphous light eruption 1, "cosmetics" 1) were re-examined 2-10 months after therapy with beta-carotene and canthaxanthine was discontinued. Dark adaptation and ERG parameters had normalized, whereas crystalline retinopathy and pigment epithelial defects showed no signs of reversibility.

Topics: beta Carotene; Canthaxanthin; Carotenoids; Dose-Response Relationship, Drug; Drug Combinations; Electroretinography; Fluorescein Angiography; Follow-Up Studies; Humans; Photosensitivity Disorders; Porphyrias; Porphyrins; Protoporphyrins; Retinal Diseases; Skin Diseases

Thirty patients who had undergone long-term treatment with carotenoids (max. 14 years and 336 g of carotenoids) were examined. Ophthalmoscopy revealed retinal crystals in 20 patients. The retinal crystals were usually located around the macula, forming a ring, and in one case they were even found in the macula itself. No deterioration of visual acuity or visual field defects were found, but there was a markedly dose-dependent prolongation of the duration of dark adaptation.

Topics: Adolescent; Adult; beta Carotene; Canthaxanthin; Carotenoids; Child; Crystallization; Dark Adaptation; Dose-Response Relationship, Drug; Drug Combinations; Electroretinography; Female; Humans; Male; Middle Aged; Retina; Retinal Diseases

A retrospective study of 14 cases of retinopathy due to canthaxanthine, a carotenoid recently used as a skin-tanning agent, revealed that several clinical factors were associated with an increased susceptibility to retinal deposits: focal epitheliopathy, ocular hypertension and, possibly, the concurrent use of beta-carotene. Age has already been established as such a factor.

Topics: Adult; Aged; beta Carotene; Canthaxanthin; Carotenoids; Drug Interactions; Female; Fluorescein Angiography; Humans; Male; Middle Aged; Ocular Hypertension; Retinal Diseases; Retrospective Studies; Skin Diseases

The retinas of twenty-six patients with protoporphyria who had received treatment with beta-carotene for periods ranging from 1 to 10 years were examined for the presence of yellow crystalline deposits, similar to those recently reported in and around the maculae of individuals ingesting the related carotenoid compound canthaxanthin. No crystalline deposits were observed in any of our patients.

Topics: Adolescent; Adult; Aged; beta Carotene; Carotenoids; Child; Crystallins; Humans; Middle Aged; Porphyrias; Protoporphyrins; Retinal Diseases; Skin Diseases