N-methyl-N-nitrosourea-induced photoreceptor apoptosis in the mouse retina.

Retinal degeneration induced by a single intraperitoneal injection of N-methyl-N-nitrosourea (MNU) in male and female albino (GRS/A and DDD/1) and colored (C57BL) mice at 7 weeks of age was examined morphologically 1, 3, 7, 14 and 21 days after the treatment. A dose of 60 mg/kg body weight evoked progressive retinal degeneration in all mice. All albino and colored mice had a comparable progression of photoreceptor cell degeneration by an apoptotic mechanism, as confirmed by morphological and TUNEL methods. Apoptosis had already taken place 1 day after the treatment and was completed by Day 7. This process resulted in a thin remnant of retina with complete loss of photoreceptor cells-21 days after the treatment. During the course of apoptosis, the pigment epithelial cells were maintained in a continuous layer in all strains of mice. In colored mice, several layers of the swollen pigment-enriched cells were seen between the inner nuclear layer and the pigment epithelial layer 14 and 21 days after the treatment. In summary, the destruction of photoreceptor cells by the apoptotic process was the mechanism by which retinal degeneration was induced by MNU.