SORBINIL PREVENTION OF DIABETIC-LIKE RETINOPATHY IN THE GALACTOSE-FEDRAT MODEL

Purpose, To determine if the retinal microangiopathies of the galactos e-fed rat model of diabetic retinopathy can be prevented with the aldo se reductase inhibitor sorbinil. Methods. Sprague-Dawley rats were fed 50% d-galactose with or without sorbinil (0.05% wt/ wt), mixed biweek ly with fresh diet. Rats in each group were examined frequently by sli t lamp and were killed after 8, 16, and 24 months. Computer-assisted m orphometry was performed on wholemounts of elastase retinal digest pre parations. Results, Cataracts developed in all galactose-fed untreated rats within 3 weeks but not in the sorbinil-treated rats even after 2 4 months. At 8 months, the galactose-fed untreated rats exhibited stat istically significant increases in the mean capillary width, the perce nt of retinal area occupied by capillaries (capillary density), and th e percent of microvascular area with capillaries >20 mu m wide (dilate d channels), compared to controls. At 16 months, the galactose-fed unt reated rats showed statistically significant increases over controls i n both total mean capillary length and density, and two of the four ra ts examined had microaneurysms. At 24 months, all the galactose-fed un treated rats had microaneurysms and extensive areas with hypercellular meshworks composed of dilated channels characteristic of intraretinal microvascular abnormalities (IRMA). By contrast, galactose-fed, sorbi nil-treated rats, at 24 months, had no IRMA and showed no statisticall y significant differences from control rats in any of the parameters m easured morphometrically. Conclusions, Ail the galactose-induced retin al microangiopathies were prevented with sorbinil. Aldose reductase in hibitors may be beneficial in ameliorating the similar vascular lesion s characteristic of human diabetic retinopathy, though the mechanism r emains obscure.