Reversal of Stage-I Sugar Cataract by Sorbinil, an Aldose Reductase Inhibitor

Abstract

Aldose reductase is implicated in the pathogenesis of sugar cataracts; therefore, inhibition of this enzyme subsequent to cataractogenesis may represent a therapeutic approach for the restoration of lens physiology despite the persistence of diabetes or galactosemia. The effect of aldose reductase inhibition subsequent to stage-I cataract formation was investigated in the galactose-maintained rat. Despite continuation of galactose feeding, the aldose reductase inhibitor, Sorbinil, a spirohydantoin, arrested further progression and promoted a reparative process. Quantitative analysis of scanning electron micrographs indicated that the afflicted lens regions were contained and their cellular components stabilized with regard to fiber hydration and interdigitation. The reparative process involved decrease in lens dulcitol, gradual recovery of fiber thickness and partial restoration of lens myo-inositol content. At this stage of cataractogenesis, despite continuance of galactose feeding, the effects of Sorbinil treatment were comparable to the reparative process achieved by restoration of a normal diet.