DEMONSTRATION THAT POLYOL ACCUMULATION IS RESPONSIBLE FOR DIABETIC CATARACT BY THE USE OF TRANSGENIC MICE EXPRESSING THE ALDOSE REDUCTASE GENE IN THE LENS
DEMONSTRATION THAT POLYOL ACCUMULATION IS RESPONSIBLE FOR DIABETIC CATARACT BY THE USE OF TRANSGENIC MICE EXPRESSING THE ALDOSE REDUCTASE GENE IN THE LENS
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DOI：
10.1073/pnas.92.7.2780
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发表时间：
1995-03-28
影响因子：
11.1
通讯作者：
CHUNG, SSM
中科院分区：
文献类型：
--
作者：
LEE, AYW;CHUNG, SK;CHUNG, SSM
醛糖还原酶（AR）与糖尿病性白内障以及其他并发症的病因有关。然而，AR在这些并发症中的作用仍然存在争议，因为最有力的支持证据来自于AR抑制剂的使用，其体内特异性无法确定。为了解决这个问题，我们开发了在其透镜上皮细胞中过表达AR的转基因小鼠，并发现它们变得容易发生糖尿病和半乳糖性白内障。当山梨糖醇脱氢酶缺陷突变也存在于这些转基因小鼠中时，山梨糖醇的积累增加，糖尿病性白内障的发展进一步加速。这些遗传学研究令人信服地证明，AR还原己糖产生的多元醇积累导致糖性白内障的形成。
Aldose reductase (AR) has been implicated in the etiology of diabetic cataract, as well as in other complications. However, the role of AR in these complications remains controversial because the strongest supporting evidence is drawn from the use of AR inhibitors for which specificity in vivo cannot be ascertained. To settle this issue we developed transgenic mice that overexpress AR in their lens epithelial cells and found that they become susceptible to the development of diabetic and galactose cataracts. When the sorbitol dehydrogenase-deficient mutation is also present in these transgenic mice, greater accumulation of sorbitol and further acceleration of diabetic cataract develop. These genetic studies demonstrated convincingly that accumulation of polyols from the reduction of hexose by AR leads to the formation of sugar cataracts.