Cataract development in gamma-glutamyl transpeptidase-deficient mice

The present study was undertaken to analyse the relationship of lens glutat hione (GSH) and light to cataract development in mice deficient in gamma -g lutamyl transpeptidase (GGT). These mice have reduced levels of cysteine an d GSI-I in the eye and develop cataracts. GGT-deficient mice raised under n ormal vivarium conditions, showed no cataractous changes at birth, but by 1 week they had developed nuclear opacities. By 3 weeks more severe cataract s develop, and lens GSH levels are approximately 6-7 % of wild type levels. By 6-11 weeks cataracts show nuclear and cortical involvement. liquefactio n and calcification. Single cell DNA electrophoresis (comet assay) demonstr ated mild DNA damage in the lens epithelium. GGT-deficient mice raised in t he dark beginning the day after conception all developed cataracts, but the se were less severe than those in GGT-deficient mice raised with normal viv arium lighting. Administration of N-acetyl cysteine (NAC) raises lens GSH a nd almost completely prevents cataract development. Our data indicate that cataract development in GGT-deficient mice is multifactorial and results Fr om exogenous damage (exposure to light), reduced lens GSH levels, and nutri tional effects secondary to low cysteine levels. (C) 2000 Academic Press.