Elsevier

Experimental Eye Research

Volume 71, Issue 6, December 2000, Pages 575-582
Experimental Eye Research

Regular Article
Cataract Development in γ-Glutamyl Transpeptidase-deficient Mice

https://doi.org/10.1006/exer.2000.0913Get rights and content

Abstract

The present study was undertaken to analyse the relationship of lens glutathione (GSH) and light to cataract development in mice deficient in γ-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.

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      GGT deficient mice were found to have severe cysteine deficiency (∼20% of WT plasma cysteine level) (Lieberman et al., 1996). Interestingly, despite high plasma GSH level in GGT deficient mice, eye and lens GSH levels are markedly reduced (∼5% of WT) (Chevez-Barrios et al., 2000). The drastic reduction of lens GSH content in GGT KO mice cannot simply be explained by impaired GSH de novo synthesis due to cysteine deficiency.

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      However, this mechanism is unlikely to be applicable to humans, given that human lenses did not show the same susceptibility of crystallin proteolysis by calpain compared with rodent lenses (Shearer et al., 1996). In the SOD, GPX1 and GGT knockout mice, no differences in GSH levels between wild type and knockout lenses were evident in both young and older animals (Chevez-Barrios et al., 2000; Spector et al., 2001; Olofsson et al., 2012). In addition, the GGT knockout lenses exhibit liquefaction and calcification (Chevez-Barrios et al., 2000), which are not features reminiscent of age related nuclear cataract.

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    Address correspondence to: Michael W. Lieberman, Department of Pathology, Baylor College of Medicine, Houston, TX 77030, U.S.A. E-mail: [email protected]

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