Cataract Development in γ-Glutamyl Transpeptidase-deficient Mice

• Published in: Experimental eye research 2000-12, Vol.71 (6), p.575-582
• Main Authors: Chévez-Barrios, Patricia, Wiseman, Amy L, Rojas, Emilio, Ou, Ching-Nan, Lieberman, Michael W
• Format: Article
• Language: English
• Subjects: Acetylcysteine - therapeutic use; Animals; Biological and medical sciences; cataract; Cataract - drug therapy; Cataract - enzymology; Cataract - etiology; cataract models; cataractogenesis; Cysteine - physiology; DNA-damage; Electrophoresis; Free Radical Scavengers - therapeutic use; gamma-Glutamyltransferase - deficiency; glutathione; Glutathione - physiology; Lens diseases; light damage; Lighting; Medical sciences; Mice; Mice, Inbred C57BL; N -acetylcysteine; Ophthalmology; transgenic mice; γ-glutamyl transpeptidase
• ISSN: 0014-4835; 1096-0007
• 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 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.