Retinal glutamate in diabetes and effect of antioxidants

Diabetes results in various biochemical abnormalities in the retina, but wh ich of these abnormalities are critical in the development of retinopathy i s not known. The aim of this study is to examine the effect of antioxidant supplementation on diabetes-induced alterations of retinal glutamate, and t o explore the inter-relationship between alterations of retinal glutamate, oxidative stress, and nitric oxide (NO) in diabetes. Glutamate was measured in the retina at 2 months of diabetes in rats receiving diets supplemented with or without a mixture of antioxidants containing ascorbic acid, Trolox , DL alpha -tocopherol acetate, N-acetyl cysteine, beta -carotene and selen ium. The relationship between glutamate, oxidative stress and NO was evalua ted using both bovine retinal endothelial cells and normal rat retina. In d iabetes, retinal glutamate was elevated by 40, thiobarbituric acid-reactive substances (TBARS) by 100, and NO by 70%, respectively. Administration of antioxidants inhibited the diabetes-induced increases in glutamate, TEARS a nd NO. Incubation of bovine retinal endothelial cells or normal rat retina with glutamate significantly increased TEARS and NO, and addition of either antioxidant (N-acetyl cysteine) or a NO synthase inhibitor prevented the g lutamate-induced elevation in oxidative stress and NO. Incubation of retina with a glutamate agonist, likewise elevated oxidative stress and NO, and m emantine inhibited such elevations. Thus, the alterations of retinal glutam ate, oxidative stress and NO appear to be inter-related in diabetes, and an tioxidant therapy may be a suitable approach to determine the roles of thes e abnormalities in the development of diabetic retinopathy. (C) 2001 Elsevi er Science Ltd. All rights reserved.