Pathophysiology Section
Prevention of Diabetic-like Cataracts:
Sugar cataracts develop more rapidly in the normal rat fed galactose (Figure 10) than in the diabetic rat, probably due to the fourfold higher affinity of AR for galactose than for glucose.
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Figure 10. Development of Galactose-induced Diabetic-like Cataract: Slit-lamp biomicroscopic images of clinical lens opacities induced in normal rats fed a 50% galactose diet for 5 to 18 days. At 5 days (upper left), in an early vacuolar stage, a foamy mass with irregular borders appears in the superficial cortex of the equatorial region. It indicates the formation of many small vacuoles. A posterior central cloudiness also appears, indicating hydropic lens fibers in the posterior subcapsular cortex. At 8 days (upper middle), many larger vacuoles have developed and the central cortex has become involved. At 10 days (upper right), there is further increase in the number and size of vacuoles. Some clear areas (seen dark in the photo) have appeared, indicating areas where liquefaction of lens contents has occurred by fusion and rupture of swollen lens fibers. At 13 days (lower left), the peripheral regions of the cortex have undergone extensive liquefaction in a radial pattern. The only enlarged vacuoles remaining are those confined to the central cortex. At 17 days (lower middle), there has been extensive liquefaction of the cortex and development of a dense opacity in the lenticular nucleus. At 18 days (lower right), all but small islands in the cortex have become liquefied, revealing the dense central opacity more clearly. Original Micrographs.
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The development of opacities in untreated galactosemic rats is so rapid and correlates so closely with the rapid increases in AR activity and polyol accumulation (Figure 1), that it is unlikely that glycation products represent an initiating factor. The white opacity characteristic of these cataracts is completely prevented by several different ARIs (Figure 11). However, yellowing occurs in the clear lenses of ARI-treated long-term galactose-fed rats, suggesting that some protein cross-linking related to glycation products may be involved in late changes, which do not progress far enough to cause loss of vision.
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Figure 11. Prevention of Diabetic-like Cataract: Slit-lamp biomicroscopy demonstrates maintenance of a clear lens in the eye of a rat fed galactose for 24 months and treated with an ARI throughout. Original micrograph.
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