Beyer-Mears A, Cruz E, Nicolas-Alexandre J, Varagiannis E
Pharmacology. 1982;24(3):193-200. doi: 10.1159/000137596.
Topical application of Sorbinil, a potent aldose reductase inhibitor, preserved lens growth, cell hydration and protein components--alpha, beta and gamma crystallins. The concomitant protective effects of Sorbinil were established on the three lenticular parameters because their quantitation offered a comprehensive index of lens integrity during galactose cataractogenesis. The fused eyelids of the rat neonate provided a natural delivery chamber, an orbital pouch, for topical administration of inhibitor to the treated lens; the contralateral pouch served as an untreated control. Protein preservation was determined by gel filtration chromatography. In galactose-maintained neonates, untreated lenses exhibited only 50% of the normal fraction-II component, whereas Sorbinil treatment maintained 95% of the protein. Likewise, quantitative analysis of scanning electron micrographs indicated that Sorbinil protected lenses against both intra- and extracellular fluid accumulation as determined by measurements of individual fiber cell thickness, density (the number of cells/10 micrometer cortex), and interdigitation. In addition, Sorbinil-treatment maintained normal growth as evidenced by radius and dry weight measurements. In normal neonates, Sorbinil had no effect on these parameters. These results indicate that changes in lens growth, fiber ultrastructure and protein components respond to aldose reductase inhibition by Sorbinil, thereby diminishing cataractogenesis.
强效醛糖还原酶抑制剂索比尼尔的局部应用可维持晶状体生长、细胞水合作用以及蛋白质成分——α、β和γ晶状体蛋白。索比尼尔对这三个晶状体参数具有协同保护作用，因为对它们的定量分析为半乳糖性白内障形成过程中晶状体完整性提供了一个综合指标。新生大鼠融合的眼睑为向受试晶状体局部给药抑制剂提供了一个天然的给药腔室——眼眶袋；对侧眼眶袋作为未处理的对照。通过凝胶过滤色谱法测定蛋白质的保留情况。在以半乳糖维持喂养的新生大鼠中，未处理的晶状体仅表现出正常Ⅱ组分的50%，而索比尼尔处理可使95%的蛋白质得以保留。同样，对扫描电子显微镜图像的定量分析表明，通过测量单个纤维细胞的厚度、密度（每10微米皮质中的细胞数量）和指状交叉，索比尼尔可保护晶状体免受细胞内和细胞外液体积聚的影响。此外，索比尼尔处理可维持正常生长，这通过半径和干重测量得到证实。在正常新生大鼠中，索比尼尔对这些参数没有影响。这些结果表明，晶状体生长、纤维超微结构和蛋白质成分的变化对索比尼尔抑制醛糖还原酶有反应，从而减少白内障的形成。
