Diabetes-induced changes in retinal NAD-redox status - Pharmacological modulation and implications for pathogenesis of diabetic retinopathy

Diabetes-induced changes in retinal metabolism and function have been linke d to increased aldose reductase activity, hypoxia or 'pseudohypoxia' (incre ase in NADH/NAD(+) attributed to increased sorbitol dehydrogenase activity) . To address this controversy, we evaluated the effects of two vasoactive c ompounds, alpha (1)-adrenoceptor antagonist prazosin and antioxidant DL-alp ha -lipoic acid, as well as sorbitol dehydrogenase inhibitor (SDI-157) and aldose reductase inhibitor (sorbinil) on retinal free mitochondrial and cyt osolic NAD(+)/NADH ratios in streptozotocin-diabetic rats. Diabetes-induced decrease in mitochondrial and cytosolic NAD(+)/NADH ratios was completely or partially corrected by prazosin and DL-alpha -lipoic acid (despite the f act that prazosin did not affect and DL-alpha -lipoic acid even further inc reased sorbitol pathway activity) as well as by sorbinil, whereas SDI-157 w as totally ineffective. Hypoxia-like metabolic changes in the diabetic reti na originate from aldose reductase, but not sorbitol dehydrogenase activity . Copyright (C) 2001 S. Karger AG, Basel.