Prevention or moderation of some ultrastructural changes in the RPE and retina of galactosemic rats by aldose reductase inhibition.
Rats were maintained on a 50% galactose diet with and without the aldose reductase inhibitor, Sorbinil, or on a normal diet of rat chow, and the retinas and retinal pigment epithelium were examined ultrastructurally at time points ranging from 4 weeks to 20 months. Several ultrastructural changes were observed in the retinal pigment epithelium and retinal capillaries of galactosemic rats that were not seen in rats on a normal diet. Only some of these changes are similar to those that have been previously noted in diabetic (glucosemic) rats. As in diabetics, galactosemic rats demonstrated thickening of the basal laminae of the retinal pigment epithelium and retinal capillaries. They also manifested vacuolization and degenerative foci in the retinal pigment epithelium that were similar, but not identical, to changes seen in diabetic rats. Each of these changes was significantly inhibited by Sorbinil. Unlike diabetics, galactosemic rats did not have dilated basal infoldings, but did have outer retinal folds and a significant increase in large-lipofuscin-like aggregates in the retinal pigment epithelium, both of which were partly prevented by Sorbinil. These data suggest that multiple mechanisms may be involved in retinal and retinal pigment epithelium changes in diabetic and galactosemic rats, and that enhanced polyol metabolism is likely to be involved in some of the changes in both.
Vinores
S A
SA
Department of Ophthalmology, University of Virginia School of Medicine, Charlottesville 22908.
Campochiaro
P A
PA
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D005693:Galactosemias / Q000473:pathology*; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000187:drug effects* / Q000648:ultrastructure; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D048289:Imidazolidines; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil