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

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          Abstract

          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<sub>2</sub>O<sub>2</sub>-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<sub>2</sub>O<sub>2</sub>, 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<sub>2</sub>O<sub>2</sub>-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.

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          Author and article information

          Journal
          OPH
          Ophthalmologica
          10.1159/issn.0030-3755
          Ophthalmologica
          S. Karger AG
          0030-3755
          1423-0267
          1997
          1997
          01 April 2010
          : 211
          : 3
          : 192-200
          Affiliations
          aEye Research Institute, Oakland University, Rochester, Mich., and, bInstitute of Chemical Toxicology, Wayne State University, Detroit, Mich., USA
          Article
          310788 Ophthalmologica 1997;211:192–200
          10.1159/000310788
          9176901
          d17ad3c7-1a76-4f79-8e6c-1746b2a07141
          © 1997 S. Karger AG, Basel

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          History
          Page count
          Pages: 9
          Categories
          Perspectives in Glaucoma Research

          Vision sciences,Ophthalmology & Optometry,Pathology
          Glutathione reductase,Hydrogen peroxide,Transgenic mice,Glutathione peroxidase,DNA strand breaks,Lens epithelium

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