Defense system of the lens against oxidative damage: Effect of oxidative challenge on cataract formation in glutathione peroxidase deficient-acatalasemic mice

The role of various enzymes involved in protecting the lens against oxidative damage by oxidants produced in vivo such as superoxide anions and, hydrogen peroxide, has been studied. Glutathione peroxidase deficiency was produced in normal and acatalasemic mice by feeding to the litters of selenium-deficient mothers a selenium-deficient diet for a period of 10 months. Glutathione peroxidase levels in the red blood cell and the lens of the selenium-deficient mice was less than 10 and 40-60% respectively, of the corresponding controls. In the red cell of the acatalasemic mice, the catalatic activity of catalase was about 3% of normal, whereas in the lens it was not detectable. However, the peroxidatic activity of catalase in the red blood cell and the lens of acatalasemic mice was comparable to the normals. When one of the protective enzymes was decreased, no compensatory increase in the other enzymes studied was observed. No lens opacity was observed in the selenium-deficient acatalasemic mice even after they were challenged with a superoxide-generating drug, phenylhydrazine. Thus, it was concluded that the lens conserves selenium (as determined by measuring selenium-dependent glutathione peroxidase) better than the red blood cells, and that glutathione peroxidase and possibly the peroxidatic activity of catalase are necessary for the protection of lens proteins and membranes against oxidative damage.