Inhibition of Sorbitol Production in Human Lenses by an Aldose Reductase Inhibitor
Clear and cataractous non-diabetic, human lenses were obtained from eye bank eyes or at the time of routine cataract extraction. Fresh lenses were assayed for glucose, sorbitol, fructose, and aldose reductase and polyol dehydrogenase activities. A significant drop in aldose reductase actvity occurs during cataractogenesis. Clear and cataractous lenses were incubated in either 5.5 mM or 35.5 mM glucose medium with or without the aldose reductase inhibitor AY22,284 (1,3-dioxo-1H-benz-[de]-isoquino-line-2-(3H) acetic acid) present in a final concentration of 4× 10−4 M. In the presence of high glucose, both the clear and cataractous lenses accumulate significant levels of sorbitol, fructose, and a high percentage gain sufficient water to rupture spontaneously. Due to the significant swelling of cataractous lenses in control medium, and the high rate of spontaneous rupture in high-glucose medium it was not possible to correlate the net sorbitol accumulation with the net change in wet weight. The presence of the aldose reductase inhibitor completely blocked net sorbitol accumulation and reduced fructose accumulation. This reduction occurred in the presence of high lenticular glucose levels and unchanged polyol dehydrogenase activity. The similarity of the human and animal lenticular responses to high glucose is striking (van Heyningen 1959a; Chylack & Kinoshita 1969). The relevance of this to’ senile’ cataract formation in diabetics and the promise of aldose reductase inhibitors as a medical treatment for cataracts are discussed.
KeywordsSugar Phenol Bicarbonate Xylose Fructose
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