Polyol metabolism of retrograde axonal transport in diabetic rat large optic nerve fiber

PURPOSE. The role of the polyol pathway metabolism in progressive impairmen t of retrograde axonal transport was evaluated in the optic nerve of rats w ith streptozotocin-induced diabetes. METHODS. Rats with streptozotocin-induced diabetes received a low (3 mg/kg body weight) or high dose (10 mg/kg body weight) of oral aldose reductase i nhibitor (ARI). At 1 and 3 months after induction of diabetes, Fluoro-Gold (FG, Chemicon, Temecula, CA) was injected into the dorsal lateral geniculat e nucleus. Percentages of FG-labeled large, medium, and small retinal gangl ion cells (RGCs) per total population were calculated in the retinas of ARI -treated diabetic, untreated diabetic, and normal control rats. RESULTS. Mean percentages of FG-labeled large RGCs per total population wer e significantly decreased in nontreated diabetic rats compared with control animals at 1 month of induced diabetes. This decrease in FG labeling was n ot observed in both the low- and high-dose ARI-treated diabetic rats. At 3 months of induced diabetes, FG labeling of both large and medium RGCs was s ignificantly decreased. This decrease was completely ameliorated by high-do se ARI treatment. CONCLUSIONS. These results indicate that diabetes affects retrograde axonal transport progressively through selective impairment of RGCs and that the polyol pathway metabolism is involved in such impairment.