PIGMENTARY DEGENERATION INDUCED BY N-METHYL-N-NITROSOUREA AND THE FATE OF PIGMENT EPITHELIAL-CELLS IN THE RAT RETINA

Pigmentary degeneration of the retina was induced by a single intraper itoneal injection of 75 mg/kg of N-methyl-N-nitrosourea (MNU) in femal e Brown-Norway colored rats at 50 days of age, which were then observe d at 24, 48 and 72 h and 7, 21, 35 and 150 days after the treatment. M NU-treated rats showed selective destruction of the photoreceptor cell s by an apoptotic mechanism 24 h after the treatment, and the destruct ion was completed by day 7. During the photoreceptor cell degeneration , proliferation of Muller cells and infiltration of macrophages was pr ominent 72 h and 21 days after the treatment, respectively. Muller cel l proliferation and macrophage infiltration corresponded to degenerati ve photoreceptor cell phagocytosis, and proliferating Muller cell proc esses responded to stabilize the damaged retina. Pigment epithelial ce ll detachment from the Bruch's membrane was seen 72 h after the treatm ent, and migration within all layers of the retina was seen at day 7 w hen photoreceptor cells were lost. At 21, 35 and 150 days after the tr eatment, lack of photoreceptor cells and deposition of pigment epithel ial cells within the retina but not in contact to vascular endothelial cells were characteristic. MNU-induced photoreceptor apoptosis follow ed by Muller cell and macrophage reaction then pigment epithelial cell s deposition within the retina partially resembles retinitis pigmentos a in humans.