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 human 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 little in vivo evidence that a mutation-induced change in the catalytic activity of SOD I is directly involved in neuronal cell death or that vulnerability to cell death is related to the level of functional/metabolic activity of cells carrying mutated SOD I. In pigmented mice carrying the G86R mutation of mouse SOD I, exposure to constant bright light for 20 days caused a diminution of electroretinographic activity and specific degeneration of photoreceptor cells, while no pathological effects were seen in transgenic littermates not exposed to bright light or in light exposed non-transgenic littermates. These findings are the first to indicate that one mechanism for neuronal cell death by mutated SOD I is use-dependent and/or related to metabolic activity, and therefore may be due to a gain in function of catalytic activities involving superoxide/hydrogen peroxide. The light-exposure pathology in this transgenic mouse model indicates an essential role for SOD I in the protection of photoreceptors from light-damage.
Mittag
T W
TW
Ophthalmology, Mount Sinai School of Medicine, Box 1183, New York, NY, 10029-6574, USA.
Bayer
A U
AU
La VAIL
M M
MM
D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000818:Animals; D004596:Electroretinography; D005260:Female; D008027:Light / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology* / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics*
D013482:Superoxide Dismutase