Effects of the aldose reductase inhibitor sorbinil on the isolated cultured rat lens.
The isolated cultured rat lens has been used to examine the effects of the aldose reductase inhibitor sorbinil on lenticular polyol accumulation and sugar cataract formation. Lenses incubated in medium containing 35 mmol/L glucose accumulated sorbitol over a seven-day period without the appearance of overt opacities. Sorbitol accumulation was inhibited in a dose response fashion by sorbinil with an IC50 of 3.1 X 10(-6) mol/L. In lenses incubated in the presence of 29.5 mmol/L xylose, xylitol accumulation was accompanied by an increase in the water content of the lens and the development of a classical sugar cataract. All of these effects could be prevented by the addition of sorbinil to the culture medium. Complete inhibition of cataract formation required greater than an 80% inhibition of the xylitol accumulation. Reversal of a preformed xylose cataract by sorbinil could be achieved if the inhibitor was added at the stage of cortical opacities (20 h). Cataract progression proceeded normally over the next 48 hours and then the lens slowly began to clear. The rate of the reversal was dependent on the dose of sorbinil.
Yeh
L A
LA
Rafford
C E
CE
Beyer
T A
TA
Hutson
N J
NJ
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002386:Cataract / Q000188:drug therapy / Q000209:etiology; D048909:Diabetes Complications; D006943:Hyperglycemia / Q000150:complications; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D048289:Imidazolidines; D007908:Lens, Crystalline / Q000032:analysis / Q000187:drug effects*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D013012:Sorbitol / Q000032:analysis; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*; D014993:Xylitol / Q000032:analysis
D007093:Imidazoles; D048289:Imidazolidines; D013012:Sorbitol; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil; D014993:Xylitol