Amelioration of diabetes-like retinal changes in galactose-fed dogs.
Diabetic retinopathy, the leading cause of blindness among young adults in the developed world, is characterized by vascular changes of the retinal capillary bed. Beagles fed a diet containing 30% galactose develop retinal vascular lesions that are similar to those observed in diabetics. These progress from initial retinal changes which include aldose-reductase-linked formation of pericyte ghosts and the subsequent development of acellular capillaries, microaneurysms, and intraretinal hemorrhages to the appearance of occluded vessels, areas of nonperfusion, and intraretinal microvascular abnormalities (IRMA) and in the final stages, the formation of fibrovascular membranes on both the retinal surface and the posterior hyaloid membrane. In prevention studies utilizing 0.5, 5.0, 10, and 16 mg/kg/day of the aldose reductase inhibitor M79175 (2-methyl-6-fluoro-spirochroman-4-5'-imidazolidine-2',4'-dione), pericyte ghost formation, and the subsequent appearance of microaneurysms, intraretinal hemorrhages, acellular capillaries associated with background retinopathy were arrested in a dose-dependent manner. Similar dose-dependent changes in the appearance of cataracts were also observed. The dog represents the first animal model to demonstrate all of the clinical and histological retinal vessel changes observed in human diabetics.
Laboratory of Ocular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892.
P F
PF
Kador
Y
Y
Takahashi
S
S
Sato
M
M
Wyman
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D002386:Cataract / Q000139:chemically induced / Q000473:pathology; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000473:pathology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005690:Galactose / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D008297:Male; D012160:Retina / Q000187:drug effects / Q000473:pathology*; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology
D007093:Imidazoles; D048289:Imidazolidines; C037070:M 79175; D000449:Aldehyde Reductase; C026411:sorbinil; D005690:Galactose