MORPHOLOGIC CHARACTERISTICS OF N-METHYL-N-NITROSOUREA-INDUCED RETINALDEGENERATION IN C57BL MICE

Morphologic characteristics of retinal degeneration induced by a singl e systemic administration of N-methyl-N-nitro-sourea (MNU) in mice was investigated. The aim was to characterize the MNU-induced retinal les ions in mice and compare them with human retinitis pigmentosa. A dose of 60 mg/kg body weight MNU, injected intraperitoneally into male and female C57BL mice, evoked progressive retinal degeneration in all trea ted mice, while control mice remained normal. An early change was phot oreceptor apoptosis followed by infiltration of macrophages and swelli ng of the pigment epithelial cells with phagosomal inclusions for apop totic photoreceptor cell removal. Loss of the majority of photorecepto r cells occurred within a week. Then, Feulgen-positive corpuscles, Ind icative of an aggregation of degenerative photoreceptor elements, vitr ead the outer limiting membrane were surrounded by Muller cell process es, and the duplication of the pigment epithelial cells sclerad the ou ter limiting membrane were seen 2 and 3 weeks after the treatment. Fin ally, the Feulgen-positive corpuscles disappeared and Muller cell proc esses were in direct contact with the continuous lining of the single layer of pigment epithelial cells. As in retinitis pigmentosa in human s, the primary event was loss of photoreceptor cells by apoptosis, but the migration of the pigment epithelial cells within the retina was n ot seen in the present model.