We have studied the regulatory actions of aldose reductase inhibition during the ONSET and REVERSAL of sugar cataractogenesis over the past 5 years; the reversal studies are still in progress. We will CONTINUE to address the 4 questions previously asked using the aldose reductase inhibitor, sorbinil, 2 in vivo cataract systems (galactose and streptozotocin) and methodology including scanning electron microscopy and gas liquid chromatography. In the reversal studies, we found that a direct correlation existed between lens myo-inositol content, cell integrity and lens transparency. Thus, a NEW OBJECTIVE is to further determine the INTERRELATIONSHIP BETWEEN MYO-INOSITOL AND THE POLYOL PATHWAY. Furthermore we will expand our study to include: 1.) a slowly progressing, genetically determined diabetic cataract model, BB RAT, 2.) a new therapeutic agent, myo-inositol and determination of its interrelationship with sorbinil to ascertain whether a synergistic effect occurs to promote the restoration of lens transparency, 3.) to analyze lens phosphatidylinositol content because myo-inositol serves as a precursor, 4.) to perform hexose transport studies to further analyze the role of sorbinil on uptake and efflux of myo-inositol, glucose and lens cation content. Thus, we will test the hypothesis that hyperglycemic concentrations of glucose competitively inhibit myo-inositol uptake, which in turn via phosphatidylinositol may lead to significant changes in cell homeostasis. The possibility of modifying the extent and rate of the reparative process by manipulation of myo-inositol and aldose reductase inhibition will be explored. Our long term objective is to enhance lens integrity in patients who exhibit various stages of diabetic cataract.
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