Efficacy of Alrestatin, an aldose reductase inhibitor, in human diabetic and nondiabetic lenses.
Immediately after cataract extraction, lenses from diabetic and nondiabetic patients were collected, classified, and assayed or incubated in high-glucose medium. The distribution of cataract types within the diabetic and nondiabetic groups was almost identical. The aldose reductase (AR) inhibitor AY22,284 (Alrestatin) was as effective in blocking sorbitol formation in diabetic as in nondiabetic lenses. While there was no difference in the level of intralenticular glucose, the diabetic lens produced significantly more sorbitol than did the nondiabetic lens. Also, the activity of polyol dehydrogenase (PD) was much lower in the diabetic population. The diabetic lenses swelled slightly more (P <.2) than nondiabetic lenses in high glucose media, and AY22,284 was effective in reducing the swelling of diabetic lenses in 35.5 mM glucose medium. While these results are preliminary, they suggest that diabetes, in some way, may confer on the human lens an increased susceptibility to osmotic stress via the sorbitol pathway. It is also reassuring to note that an AR inhibitor is no less effective in blocking the more active AR in the diabetic than in the nondiabetic lens. The therapeutic implications of this are discussed.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D002386:Cataract / Q000150:complications*; D002387:Cataract Extraction; D048909:Diabetes Complications; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D007908:Lens, Crystalline / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010088:Oxidoreductases / Q000032:analysis; D013012:Sorbitol / Q000378:metabolism; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D007546:Isoquinolines; D013012:Sorbitol; C016212:alrestatin; D010088:Oxidoreductases; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D005947:Glucose