Vn. Reddy et al., PEROXIDE-INDUCED DAMAGE IN LENSES OF TRANSGENIC MICE WITH DEFICIENT AND ELEVATED LEVELS OF GLUTATHIONE-PEROXIDASE, Ophthalmologica, 211(3), 1997, pp. 192-200
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 H2O2-indu
ced damage. The effects of peroxide on cultured lenses were determined
by using light and transmission electron microscopy to evaluate morph
ological changes occurring in the epithelium and superficial cortex of
the central and equatorial regions of the lens. DNA single-strand bre
aks in the epithelium were also examined. Following a 30-min exposure
to 25 mu M H2O2, lenses from normal animals showed distinct changes in
the morphology of both the epithelium and superficial cortex. The dam
age to these cells was extensive in lenses of gene knockout mice in wh
ich activity of GSHPx was undetectable. In marked contrast, lenses of
transgenic mice, which had 5-fold higher activities of GSHPx, were abl
e to resist the cytotoxic effects. Similar to damage to cell morpholog
y, the extent of DNA strand breaks was significantly lower (40% of con
trol) in H2O2-exposed lenses as compared to normal lenses while DNA da
mage in gene knockout lenses was 5 times greater than that of GSHPx-ri
ch transgenic lenses. The present studies extend our previous findings
on the role of the glutathione redox cycle in the detoxification of p
eroxide and demonstrate that an increase in GSHPx activity protects th
e lens against peroxide-induced changes in cell morphology and DNA str
and breaks.