We have studied the regulatory actions of aldose reductase inhibition during the onset of sugar cataractogenesis; however, little information exists in the literature concerning the possible regulation of cataractogenesis subsequent to cataract formation. Aldose reductase inhibition may enhance lens integrity in human diabetic patients who already exhibit sugar cataracts. Therefore, the specific aims of our proposed study are to determine whether aldose reductase inhibition is capable of arresting further cataractogenesis and promoting a reparative process. If the latter is achieved, then the nature and extent of the reparative process will be ascertained for specific regions within an individual lens. Previously we analyzed the process of cataract reversal using dietary regulation. Three factors which influenced the reparative process were the rate, duration and extent of cataractogenesis within a specific lens region prior to the initiation of a normal diet. Therefore, we will employ in vivo systems which exhibit markedly different rates of cataractogenesis: the galactose-fed rat which exhibits a rapid rate and a slower cataract developed by the streptozotocin-induced diabetic rat. These animals will be maintained until a cataract specific stage (I to V) has been obtained and classified using the Sipple slit-lamp protocol. To provide a comprehensive index of total and regional lens integrity, four measures, fiber hydration, cellular interdigitation, soluble protein components and polyol levels, will be quantitated and correlated with the slit-lamp classification and blood sugar levels prior to initiation of an aldose reductase inhibitor. For animals receiving an aldose reductase inhibitor, the duration of treatment will vary in direct proportion to the duration of the previously untreated cataract; then similar lens measures will be performed to determine the concomitant protective effects. The possibility of modifying the extent and rate of the reparative process by manipulation of diet and aldose reductase inhibitors 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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