Sorbinil prevention of diabetic-like retinopathy in the galactose-fed rat model.
OBJECTIVE
To determine if the retinal microangiopathies of the galactose-fed rat model of diabetic retinopathy can be prevented with the aldose reductase inhibitor sorbinil.


METHODS
Sprague-Dawley rats were fed 50% d-galactose with or without sorbinil (0.05% wt/wt), mixed biweekly with fresh diet. Rats in each group were examined frequently by slit lamp and were killed after 8, 16, and 24 months. Computer-assisted morphometry was performed on wholemounts of elastase retinal digest preparations.


RESULTS
Cataracts developed in all galactose-fed untreated rats within 3 weeks but not in the sorbinil-treated rats even after 24 months. At 8 months, the galactose-fed untreated rats exhibited statistically significant increases in the mean capillary width, the percent of retinal area occupied by capillaries (capillary density), and the percent of microvascular area with capillaries > 20 microns wide (dilated channels), compared to controls. At 16 months, the galactose-fed untreated rats showed statistically significant increases over controls in both total mean capillary length and density, and two of the four rats examined had microaneurysms. At 24 months, all the galactose-fed untreated rats had microaneurysms and extensive areas with hypercellular meshworks composed of dilated channels characteristic of intraretinal microvascular abnormalities (IRMA). By contrast, galactose-fed, sorbinil-treated rats, at 24 months, had no IRMA and showed no statistically significant differences from control rats in any of the parameters measured morphometrically.


CONCLUSIONS
All the galactose-induced retinal microangiopathies were prevented with sorbinil. Aldose reductase inhibitors may be beneficial in ameliorating the similar vascular lesions characteristic of human diabetic retinopathy, though the mechanism remains obscure.
Robison
W G
WG
National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Laver
N M
NM
Jacot
J L
JL
Glover
J P
JP
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002196:Capillaries / Q000473:pathology; D002386:Cataract / Q000139:chemically induced / Q000517:prevention & control; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005690:Galactose; D007091:Image Processing, Computer-Assisted; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D048289:Imidazolidines; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology
D004791:Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D000449:Aldehyde Reductase; C026411:sorbinil; D005690:Galactose