Pigmentary degeneration indwed by N‐methyl‐N‐nitrosourea and the fate of pigment epithelial cells in the rat retina

Abstract

Pigmentary degeneration of the retina was induced by a single intraperitoneal injection of 75 mg/kg of N-methyl-N-nitrosourea (MNU) in female Brown-Norway colored rats at 50 days of age, which were then observed at 24, 48 and 72 h and 7, 21, 35 and 150 days after the treatment. MNU-treated rats showed selective destruction of the photoreceptor cells by an apoptotic mechanism 24 h after the treatment, and the destruction was completed by day 7. During the photoreceptor cell degeneration, proliferation of Müller cells and infiltration of macrophages was prominent 72 h and 21 days after the treatment, respectively. Müller cell proliferation and macrophage infiltration corresponded to degenerative photoreceptor cell phagocytosis, and proliferating Müller cell processes responded to stabilize the damaged retina. Pigment epithelial cell detachment from the Bruch's membrane was seen 72 h after the treatment, and migration within all layers of the retina was seen at day 7 when photoreceptor cells were lost. At 21, 35 and 150 days after the treatment, lack of photoreceptor cells and deposition of pigment epithelial cells within the retina but not in contact to vascular endothelial cells were characteristic. MNU-induced photoreceptor apoptosis followed by Müller cell and macrophage reaction then pigment epithelial cells deposition within the retina partially resembles retinitis pigmentosa in humans.