Age-specific and Dose-dependent Retinal Dysplasia and Degeneration Induced by a Single Intraperitoneal Administration of N-Methyl-N-nitrosourea to Rats

The morphologic response of the rat retina at different ages to the various doses of the alkylating agent N-methyl-N-nitrosourea (MNU) was examined. MNU at the dose of 35, 50, 75, 90, and/or 105 mg/kg was injected intraperitoneally (ip) to male and female Sprague-Dawley and Lewis rats at 0, 21, 50, and 150 days of age, and the retinas were examined 7 or 21 days after the treatment. In both strains of rats, regardless of gender, MNU evoked age-specific and dose-dependent retinal lesions. When ≥ 50 mg/kg MNU were administered at day 0, retinal dysplasia characterized by rosette formation was found in the outer neuroblastic/nuclear layer above the continuous lining single layer of pigment epithelial cells. The severity of the lesion was not dose-related. When > 90 mg/kg, > 50 mg/kg and ≥ 35 mg/kg MNU were administered at day 21, 50, and 150, respectively, retinal degeneration characterized by selective photoreceptor cell loss due to apoptosis with disorganized pigment epithelial cells was found in all rats. Thus, the sensitivity of photoreceptor cells in the development of retinal degeneration induced by MNU increased in parallel with aging.