Abnormalities of retinal metabolism in diabetes or experimental galactosemia. VI. Comparison of retinal and cerebral cortex metabolism, and effects of antioxidant therapy

Metabolic abnormalities observed in retina and in cerebral cortex were comp ared in diabetic rats and experimentally galactosemic rats. Diabetes or exp erimental galactosemia of 2 months duration significantly increased oxidati ve stress in retina, as shown by elevation of retinal thiobarbituric acid r eactive substances (TEARS) and subnormal activities of antioxidant defense enzymes, but had no such effect in the cerebral cortex. Activities of sodiu m potassium adenosine triphosphatase [(Na,K)-ATPase] and calcium ATPase bec ame subnormal in retina as well as in cerebral cortex. In contrast, protein kinase C (PKC) activity was elevated in retina but not in cerebral cortex in the same hyperglycemic rats. Dietary supplementation with an antioxidant mixture (containing ascorbic acid, Trolox, alpha-tocopherol acetate, N-ace tyl cysteine, beta-carotene, and selenium) prevented the diabetes- induced and galactosemia-induced elevation of retinal oxidative stress, the elevati on of retinal PKC activity and the decrease of retinal ATPases. In cerebral cortex, administration of the antioxidant diet also prevented the diabetes -induced decreases in (Na,K)-ATPase and calcium ATPases, but had no effect on TEARS and activities of PKC and antioxidant-defense enzymes. The results indicate that retina and cerebral cortex differ distinctly in their respon se to elevation of tissue hexose, and that cerebral cortex is more resistan t than retina to diabetes-induced oxidative stress. The greater resistance to oxidative stress in cerebral cortex, as compared to retina, is consisten t with the resistance of cerebral cortex to microvascular disease in diabet es, and with a hypothesis that oxidative stress contributes to microvascula r disease in diabetes. Dietary supplementation with these antioxidants offe rs a means to inhibit multiple hyperglycemia-induced retinal metabolic abno rmalities. (C) 1998 Elsevier Science Inc.