DOSE-DEPENDENT REDUCTION OF RETINAL VESSEL CHANGES ASSOCIATED WITH DIABETIC-RETINOPATHY IN GALACTOSE-FED DOGS BY THE ALDOSE REDUCTASE INHIBITOR M79175

The onset and progression of retinal vascular changes associated with early diabetic retinopathy has been delayed in beagles fed 30% galacto se diet for 38 months by treatment with the aldose reductase inhibitor M79175 uoro-spirochroman-4-5'-imidazolidine-2',4'-dione). Forty 9-mon th old male beagles were fed a daily diet containing either 30% non-nu trient filler or 30% galactose. One group of galactose-fed dogs was un treated while the others received M79175 at an average group dose of e ither 10 or 16 mg/kg/day. After 38 months one eye from 4 dogs from eac h group was enucleated and the isolated retinal vasculatures were obje ctively evaluated using an Olympus Cue-3 color image analysis system. Measurements of endothelium/pericyte (E/P) ratios, pericyte ghosts/100 0 cells, pericytes and endothelial densities, and % acellularity per a rea and % acellularity per capillary length were conducted on a 0.1 mm square area surrounding the midpoints of 12 previously defined subreg ions. With the exception of endothelial densities which were not chang ed in galactose-fed dogs, M79175 treatment resulted in smaller changes in all parameters examined with the E/P ratio in dogs treated with 16 mg/kg/day M79175 not significantly different from that of age-matched non-galactose-fed dogs. These studies indicate that aldose reductase inhibitors provide dose-dependent protection against pericyte degenera tion and subsequent microaneurysms formation.