Lin L R, Reddy V N, Giblin F J, Kador P F, Kinoshita J H
Eye Research Institute, Oakland University, Rochester, MI 48309-4401.
Exp Eye Res. 1991 Jan;52(1):93-100. doi: 10.1016/0014-4835(91)90132-x.
Human lens epithelial (HLE) cells in tissue culture accumulated significant levels of galactitol when they were cultured for 72 hr in medium containing 30 mM D-galactose. Polyol accumulation was accompanied by the appearance of vacuoles as seen by transmission electron microscopy. The number and size of intracellular vacuoles increased when the culture period was extended to 7 days. In addition, polyol accumulation was accompanied by loss of myoinositol. None of these changes occurred in cells exposed to 30 M L-galactose which is not a substrate for aldose reductase. The accumulation of galactitol, intracellular vacuole formation and loss of myoinositol observed in D-galactose-exposed cells were prevented by the inclusion of the aldose reductase inhibitor, sorbinil, in the culture medium. Comparison of the relative efficacies of two aldose reductase inhibitors indicate that AL 1576 is nearly 20 times more potent than sorbinil in inhibiting the human lens enzyme. It is concluded that vacuole formation in HLE cells is due to the osmotic effect of polyol formation brought about by the action of aldose reductase and that the etiology of human diabetic cataract may also involve the polyol pathway.
在组织培养中，人晶状体上皮（HLE）细胞在含有30 mM D-半乳糖的培养基中培养72小时后，积累了大量的半乳糖醇。透射电子显微镜观察显示，多元醇积累伴随着液泡的出现。当培养期延长至7天时，细胞内液泡的数量和大小增加。此外，多元醇积累伴随着肌醇的丢失。暴露于30 M L-半乳糖（不是醛糖还原酶的底物）的细胞未发生这些变化。在培养基中加入醛糖还原酶抑制剂索比尼尔可防止在暴露于D-半乳糖的细胞中观察到的半乳糖醇积累、细胞内液泡形成和肌醇丢失。两种醛糖还原酶抑制剂相对效力的比较表明，AL 1576在抑制人晶状体酶方面的效力比索比尼尔高近20倍。得出结论，HLE细胞中的液泡形成是由于醛糖还原酶作用导致多元醇形成的渗透效应，并且人类糖尿病性白内障的病因可能也涉及多元醇途径。
