Chévez-Barrios P, Wiseman A L, Rojas E, Ou C N, Lieberman M W
Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
Exp Eye Res. 2000 Dec;71(6):575-82. doi: 10.1006/exer.2000.0913.
The present study was undertaken to analyse the relationship of lens glutathione (GSH) and light to cataract development in mice deficient in gamma-glutamyl transpeptidase (GGT). These mice have reduced levels of cysteine and GSH in the eye and develop cataracts. GGT-deficient mice raised under normal vivarium conditions, showed no cataractous changes at birth, but by 1 week they had developed nuclear opacities. By 3 weeks more severe cataracts develop, and lens GSH levels are approximately 6-7% of wild type levels. By 6-11 weeks cataracts show nuclear and cortical involvement, liquefaction and calcification. Single cell DNA electrophoresis (comet assay) demonstrated mild DNA damage in the lens epithelium. GGT-deficient mice raised in the dark beginning the day after conception all developed cataracts, but these were less severe than those in GGT-deficient mice raised with normal vivarium lighting. Administration of N -acetyl cysteine (NAC) raises lens GSH and almost completely prevents cataract development. Our data indicate that cataract development in GGT-deficient mice is multifactorial and results from exogenous damage (exposure to light), reduced lens GSH levels, and nutritional effects secondary to low cysteine levels.
本研究旨在分析γ-谷氨酰转肽酶（GGT）缺乏的小鼠晶状体谷胱甘肽（GSH）与光照和白内障形成之间的关系。这些小鼠眼部的半胱氨酸和GSH水平降低，并会发展为白内障。在正常饲养条件下饲养的GGT缺乏小鼠出生时无白内障变化，但1周时出现核混浊。3周时会发展为更严重的白内障，晶状体GSH水平约为野生型水平的6 - 7%。6 - 11周时白内障出现核及皮质受累、液化和钙化。单细胞DNA电泳（彗星试验）显示晶状体上皮有轻度DNA损伤。从受孕后第二天开始在黑暗中饲养的GGT缺乏小鼠均发展为白内障，但比在正常饲养光照条件下饲养的GGT缺乏小鼠的白内障程度轻。给予N - 乙酰半胱氨酸（NAC）可提高晶状体GSH水平并几乎完全预防白内障的形成。我们的数据表明，GGT缺乏小鼠白内障的形成是多因素的，由外源性损伤（暴露于光照）、晶状体GSH水平降低以及半胱氨酸水平低所致的营养效应共同引起。
