The Effect of Aging on Glutathione Peroxidase-I Knockout Mice—Resistance of the Lens to Oxidative Stress

• Published in: Experimental eye research Vol. 72; no. 5; pp. 533 - 545
• Main Authors: Spector, Abraham, Kuszak, Jer R, Ma, Wanchao, Wang, Ren-Rong
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2001
• Subjects: Aging - physiology; Animals; Buttocks; choline transport; Glutathione Peroxidase - genetics; Glutathione Peroxidase - physiology; H2O2; Hydrogen Peroxide - metabolism; Lens, Crystalline - physiology; light and electron microscopy; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Electron; Organ Culture Techniques; Oxidative Stress - physiology; photochemical stress; tertiary butyl hydroperoxide; thiol status; choline transport; H2O2; light and electron microscopy; photochemical stress; tertiary butyl hydroperoxide; thiol status
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1006/exer.2001.0980

Populations of control, C, and glutathione peroxidase-1 (GPx-1) knockout mice, K, were studied over a period of 2 years. No significant difference was observed between the C and K populations with respect to longevity, vitality, weight, lens biochemistry or morphology based on light and electron microscopy. It was concluded that under normal animal room barrier facilities, GPx-1 is not required. Furthermore, C and K lenses placed in organ culture and observed over a 24hr period were indistinguishable. Organ cultured C lenses degraded medium H2O2levels at only a slightly greater rate than K lenses and this did not appear to change with age. However, tertiary butyl hydroperoxide (TBHP) was degraded less effectively by K lenses and this deficiency increased with age. No indication of change in redox non-protein SH (equivalent to GSH) status was observed between C and K whole lenses or epithelial cell fractions. With H2O2stress, the drop in C and K non-protein SH was comparable and there was little change with age. Examination of the impact of photochemical stress with 1.5μM riboflavin and 4% O2upon choline transport indicated considerable damage with both C and K lenses, but little difference between the two populations until 1 or 2 years of age when the K lenses appear more vulnerable. With TBHP, the detrimental effect on the K lenses is greater and is observed earlier than with photochemical stress suggesting that the K lens membrane function is more susceptible to phospholipid hydroperoxide stress than are C lenses. Light and electron microscopy of the oxidative stressed lenses indicates significant damage which was generally somewhat greater in the K lenses. TBHP was a more potent oxidant than photochemically generated oxidants particularly at the anterior pole. The overall results suggest that under normal conditions, at any age, the lens does not require the presence of GPx-1 but depending on the type of oxidative stress, the enzyme may significantly contribute to its defense and this dependency may increase with age.