Aldose reductase in diabetic complications of the eye.
Aldose reductase (AR) appears to initiate the cataractous process in galactosemic and diabetic animals. Sugars in excess are converted to polyols by lens AR. In sugar cataracts, polyols accumulate to levels substantial enough to cause a hypertonicity leading to lens fiber swelling. All other changes appear secondary to polyol accumulation and lens swelling. The development of sugar cataracts can be duplicated in organ culture. In culture, the various changes that occur were minimized or did not occur when inhibitors of AR were included in the medium. Moreover, AR inhibitors were shown to effectively delay the onset of sugar cataract development in animals. A defect in the corneal epithelium of diabetics became apparent in vitrectomy. One manifestation of this problem was the delay in the reepithelialization of denuded corneas. In examining this problem experimentally, the epithelium was removed from the corneas of diabetic and normal rats. The regeneration of epithelium in corneas of diabetic rats required a longer period than in the normal. The possibility that AR, active in the epithelium, was involved in this phenomenon was investigated. The corneal epithelium was removed from both eyes of a diabetic rat. One eye was treated topically with the AR inhibitor CP-45,634 while the other served as control. The eye treated with CP-45,635 regenerated epithelium much more quickly than the untreated eye. Other AR inhibitors had similar beneficial effects.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002386:Cataract / Q000139:chemically induced / Q000201:enzymology*; D002417:Cattle; D002839:Chromans; D003315:Cornea / Q000601:surgery; D048909:Diabetes Complications; D003930:Diabetic Retinopathy / Q000601:surgery; D004848:Epithelium / Q000502:physiology; D005128:Eye Diseases / Q000201:enzymology* / Q000209:etiology; D005260:Female; D004376:Galactitol / Q000378:metabolism; D005690:Galactose; D006801:Humans; D007093:Imidazoles; D048289:Imidazolidines; D007908:Lens, Crystalline / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D011108:Polymers / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D012038:Regeneration / Q000187:drug effects; D012160:Retina / Q000201:enzymology; D012377:Rodentia / Q000378:metabolism; D012584:Sciatic Nerve / Q000378:metabolism; D013012:Sorbitol / Q000378:metabolism; D013401:Sugar Alcohol Dehydrogenases / Q000378:metabolism*; D014993:Xylitol / Q000378:metabolism
D002839:Chromans; D007093:Imidazoles; D048289:Imidazolidines; D011108:Polymers; C024617:polyol; D004376:Galactitol; D013012:Sorbitol; D009249:NADP; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C023142:polyol dehydrogenase (NADP); C026411:sorbinil; D014993:Xylitol; D005690:Galactose