The effect of aging on glutathione peroxidase-1 knockout mice - Resistanceof the lens to oxidative stress

Populations of control, C, and glutathione peroxidase-l (GPx-1) knockout mi ce, K, were studied over a period of 2 years. No significant difference was observed between the C and It populations with respect to longevity, vital ity, weight, lens biochemistry or morphology based on light and electron mi croscopy. It was concluded that under normal animal room barrier facilities , GPx-1 is not required. Furthermore, C and ii lenses placed in organ cultu re and observed over a 24 hr period were indistinguishable. Organ cultured C lenses degraded medium H2O2 levels 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 IC lenses and this d eficiency increased with age. No indication of change in redox nonprotein S H (equivalent to GSH) status was observed between C and IC whole lenses or epithelial cell fractions. With H2O2 stress, the drop in C and It non-prote in SH was comparable and there was little change with age. Examination of t he impact of photochemical stress with 1.5 muM riboflavin and 4 % O-2 upon choline transport indicated considerable damage with both C and IC 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 It lenses is greater and is observed earlier than with photochemica l stress suggesting that the IC 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 wh ich was generally somewhat greater in the K lenses. TBHP was a more potent oxidant than photochemically generated oxidants particularly at the anterio r pole. The overall results suggest that under normal conditions, at any ag e, the lens does not require the presence of GPx-1 but depending on the typ e of oxidative stress, the enzyme may significantly contribute to its defen se and this dependency may increase with age. (C) 2001 Academic Press.