Cataract development in gamma-glutamyl transpeptidase-deficient mice.
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.
Chévez-Barrios
P
P
Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
Wiseman
A L
AL
Rojas
E
E
Ou
C N
CN
Lieberman
M W
MW
D000111:Acetylcysteine / Q000627:therapeutic use; D000818:Animals; D002386:Cataract / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology; D003545:Cysteine / Q000502:physiology; D004586:Electrophoresis; D016166:Free Radical Scavengers / Q000627:therapeutic use; D005978:Glutathione / Q000502:physiology; D008029:Lighting; D051379:Mice; D008810:Mice, Inbred C57BL; D005723:gamma-Glutamyltransferase / Q000172:deficiency*
D016166:Free Radical Scavengers; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine