Light-induced retinal damage in mice carrying a mutated SOD I gene

Transgenic mice expressing mutated mouse Cu/Zn superoxide dismutase (SOD I) , corresponding to a mutation associated with familial amyotrophic lateral sclerosis, develop a fatal motorneuron degeneration that resembles the huma n disease, The biochemical properties of some mutant SOD I enzymes indicate that a gain of catalytic functions, (such as increased peroxidase activity ) may be the pathologic factor(s). However, at the present time there is li ttle in vivo evidence that a mutation-induced change in the catalytic activ ity of SOD I is directly involved in neuronal cell death or that vulnerabil ity to cell death is related to the level of functional/metabolic activity of cells carrying mutated SOD I. In pigmented mice carrying the G86R mutati on of mouse SOD I, exposure to constant bright light for 20 days caused a d iminution of electroretinographic activity and specific degeneration of pho toreceptor cells, while no pathological effects were seen in transgenic lit termates not exposed to bright light or in light exposed nontransgenic litt ermates. These findings are the first to indicate that one mechanism for ne uronal cell death by mutated SOD I is use-dependent and/or related to metab olic activity, and therefore mag be due to a gain in function of catalytic activities involving superoxide/hydrogen peroxide. The light-exposure patho logy in this transgenic mouse model indicates an essential role for SOD I i n the protection of photoreceptors from light-damage. (C) 1999 Academic Pre ss.