Peroxide-Induced Damage in Lenses of Transgenic Mice with Deficient and Elevated Levels of Glutathione Peroxidase

• Published in: Ophthalmologica (Basel) Vol. 211; no. 3; pp. 192 - 200
• Main Authors: Reddy, V.N., Lin, L.R., Ho, Y.-S., Magnenat, J.-L., Ibaraki, N., Giblin, F.J., Dang, L.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Basel, Switzerland Karger 01.01.1997
• Subjects: Animals; Biological and medical sciences; DNA Damage - drug effects; Electrophoresis, Agar Gel; Epithelium - drug effects; Epithelium - enzymology; Epithelium - pathology; Eye and associated structures. Visual pathways and centers. Vision; Female; Fluorescent Antibody Technique, Direct; Fundamental and applied biological sciences. Psychology; Glutathione Peroxidase - deficiency; Glutathione Peroxidase - physiology; Hydrogen Peroxide - toxicity; Lens, Crystalline - drug effects; Lens, Crystalline - enzymology; Lens, Crystalline - pathology; Male; Mice; Mice, Knockout; Mice, Transgenic; Organ Culture Techniques; Oxidants - toxicity; Perspectives in Glaucoma Research; Vertebrates: nervous system and sense organs; Glutathione peroxidase; Hydrogen peroxide; Lens epithelium; Glutathione reductase; DNA strand breaks; Transgenic mice; Cell oxidation; Enzyme; Rodentia; Experimental study; Vertebrata; Mammalia; Peroxidases; Mouse; Animal; Lens; Physiology; Oxidoreductases; Oxidation protection
• ISSN: 0030-3755; 1423-0267
• DOI: 10.1159/000310788

Transgenic mice with elevated glutathione peroxidase (GSHPx) activity and gene knockout animals with a deficiency of the enzyme were used to investigate the role of GSHPx in defending the lens against H 2 O 2 -induced damage. The effects of peroxide on cultured lenses were determined by using light and transmission electron microscopy to evaluate morphological changes occurring in the epithelium and superficial cortex of the central and equatorial regions of the lens. DNA single-strand breaks in the epithelium were also examined. Following a 30-min exposure to 25 µM H 2 O 2 , lenses from normal animals showed distinct changes in the morphology of both the epithelium and superficial cortex. The damage to these cells was extensive in lenses of gene knockout mice in which activity of GSHPx was undetectable. In marked contrast, lenses of transgenic mice, which had 5-fold higher activities of GSHPx, were able to resist the cyto-toxic effects. Similar to damage to cell morphology, the extent of DNA strand breaks was significantly lower (40% of control) in H 2 O 2 -exposed lenses as compared to normal lenses while DNA damage in gene knockout lenses was 5 times greater than that of GSHPx-rich transgenic lenses. The present studies extend our previous findings on the role of the glutathione redox cycle in the detoxification of peroxide and demonstrate that an increase in GSHPx activity protects the lens against peroxide-induced changes in cell morphology and DNA strand breaks.