Abnormalities of retinal metabolism in diabetes and experimental galactosemia VII. Effect of long-term administration of antioxidants on the development of retinopathy

Antioxidants were administered to diabetic rats and experimentally galactos emic rats to evaluate the ability of these agents to inhibit the developmen t of diabetic retinopathy. Alloxan diabetic rats and nondiabetic rats that were fed 30% galactose randomly received standard diets or the diets supple mented with ascorbic acid and alpha -tocopherol (vitamins C+E diet) or a mo re comprehensive mixture of antioxidants (multi-antioxidant diet), includin g Trolox, alpha -tocopherol, N-acetyl cysteine, ascorbic acid, beta -carote ne, and selenium. Diabetes or galactose feeding of at least 12 months resul ted in pericyte loss, acellular capillaries, and basement membrane thickeni ng. Compared with diabetic controls, the development of acellular capillari es was inhibited by 50% (P < 0.05) in diabetic rats that received supplemen tal vitamins C+E, and the number of pericyte ghosts tended to be reduced. T he vitamins C+E supplement had no beneficial effect in galactosemic rats, b ut these rats consumed only approximately half as much of the antioxidants as the diabetic rats. The multi-antioxidant diet significantly inhibited (s imilar to 55-65%) formation of both pericyte ghosts and acellular capillari es in diabetic rats and galactosemic rats (P < 0.05 vs. controls), without affecting the severity of hyperglycemia. Parameters of retinal oxidative st ress, protein kinase C activity, and nitric oxides remained elevated for at least I year of hyperglycemia, and these abnormalities were normalized by multi-antioxidant therapy. Thus, longterm administration of antioxidants ca n inhibit the development of the early stages of diabetic retinopathy, and the mechanism by which this action occurs warrants further investigation, S upplementation with antioxidants can offer an achievable and inexpensive ad junct therapy to help inhibit the development of retinopathy in diabetes.