TIME-SPECIFIC ACTION OF N-METHYL-N-NITROSOUREA IN THE OCCURRENCE OF RETINAL DYSPLASIA AND RETINAL DEGENERATION IN NEONATAL MICE

The morphologic response of neonatal mouse retina to the alkylating ag ent N-methyl-N-nitrosourea (MNU) was examined at different periods of retinal development, A dose of 60 mg/kg N-methyl-N-nitrosourea was inj ected intraperitoneally to neonatal C57BL mice at 0, 3, 5, 8, 11, 14, 17, and 20 days of age and to C3H mice at 0 days of age, and the retin as were examined sequentially, In the C57BL mice, MNU evoked a time-de pendent occurrence of retinal dysplasia and retinal degeneration, With MNU treatment at day 0 and day 3 (the stage of retinal cell prolifera tion), retinal dysplasia characterized by the progressive disorganizat ion of neuroblasts, which led to the formation of rosettes, was found in the outer neuroblastic/nuclear layer above the normal pigment epith elial cells during days 8-20, but decreased at day 50, The rosettes we re surrounded by photoreceptor segments and Muller cell processes, and by photoreceptor nuclei, The MNU response was related to retinal diff erentiation; following MNU treatment at day 5 or 8 (the stage of retin al cell differentiation) the cells were much less sensitive (i.e. no r etinal response was found). However, with MNU treatment at days 11, 14 , 17, and 20 (after cellular differentiation), retinal degeneration ch aracterized by selective photoreceptor apoptosis was seen, These resul ts suggest that there is a critical period for the time of MNU adminis tration in the development of mouse retinal lesions. In C3H (rd/rd) mi ce, MNU treatment at day 0 resulted in retinal degeneration with only slight rosette formation at the peripheral retina.