Abstract
Diabetes-induced changes in retinal metabolism and function have been linked to increased aldose reductase activity, hypoxia or ‘pseudohypoxia’ (increase in NADH/NAD<sup>+</sup> attributed to increased sorbitol dehydrogenase activity). To address this controversy, we evaluated the effects of two vasoactive compounds, α<sub>1</sub>-adrenoceptor antagonist prazosin and antioxidant DL-α-lipoic acid, as well as sorbitol dehydrogenase inhibitor (SDI-157) and aldose reductase inhibitor (sorbinil) on retinal free mitochondrial and cytosolic NAD<sup>+</sup>/NADH ratios in streptozotocin-diabetic rats. Diabetes-induced decrease in mitochondrial and cytosolic NAD<sup>+</sup>/NADH ratios was completely or partially corrected by prazosin and DL-α-lipoic acid (despite the fact that prazosin did not affect and DL-α-lipoic acid even further increased sorbitol pathway activity) as well as by sorbinil, whereas SDI-157 was totally ineffective. Hypoxia-like metabolic changes in the diabetic retina originate from aldose reductase, but not sorbitol dehydrogenase activity.
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