Inhibitory effect of orally administered aldose reductase inhibitor SNK-860 on corneal polyol accumulation in galactose-fed rats

Background: Diabetic keratopathy, frequently observed after vitreous surger y, has been thought to be related to the aldose reductase-catalyzed reactio n. However, few reports have been published on the chronological changes in polyol accumulation and the effect of the aldose reductase inhibitor in th e corneal epithelium or endothelium of galactosemic rats. Consequently, the polyol accumulation in corneal epithelium and endothelium with stroma of 5 0% galactose-fed rats and the preventive effect of an aldose reductase inhi bitor, SNK-860, were biochemically analyzed. Methods: Four-week-old male Sprague-Dawley rats were fed a 50% galactose di et without supplement or supplemented with a low (3 mg/kg b.w.) or high (30 mg/kg b.w.) dose of SNK-860 (Sanwa Kagaku Kenkyusho, Japan), or a normal d iet. Polyol contents in the corneal epithelium or endothelium with stroma w ere individually measured using gas-liquid chromatography. Results: Polyol in corneal epithelia accumulated quickly in the 1st week, reached a maximum at the 3rd week of feeding and then gradually decreased. Low- and high-dos e SNK-860 treatment significantly inhibited polyol accumulation in the epit helium and endothelium with stroma, respectively. Changing to the normal or SNK-860 supplemented diets significantly inhibited polyol accumulation. Co nclusion: This finding indicates that oral administration of a new aldose r eductase inhibitor, SNK-860, or systematic treatment of diabetes may be eff ective in preventing polyol pathway-induced corneal damage by quickly reduc ing the polyol level.