Structural changes in retinal and choroidal vasculature following N-methyl-N-nitrosourea-induced retinal degeneration in rats

The DNA alkylating agent N-methyl-N-nitrosourea (MNU) damages photoreceptor cells and is widely used to create animal models of retinitis pigmentosa. To better understand the cellular interaction between photoreceptor and vascular cells, we examined the time course of structural changes in the retinal and choroidal vasculature following MNU-induced photoreceptor cell degeneration in rats. Adult male Sprague-Dawley rats were used in this study. The eyes were enucleated 1, 3, 7, and 14 days after intraperitoneal injection of MNU (25, 50, and 75 mg/kg) or saline. The thickness of the retinal layers, number of cells in the ganglion cell layer, and vascular densities of the retinal and choroidal vasculature were measured. A time-dependent reduction in the thickness of the outer retina was observed in MNU (50 and 75 mg/kg)-treated rats. Significant capillary loss was observed in retinal superficial and deep vascular plexuses 7 days after MNU injection, which further progressed at 14 days. The reduction in vascular density was greater in the deep vascular plexus than in the superficial vascular plexus. Capillary degeneration was also observed in the choroidal vasculature after MNU injection. Damage to the choriocapillaris was more severe than that to the larger vessels in the outer choroid. After MNU injection, vascular endothelial growth factor (VEGF) expression in the outer nuclear layer and retinal pigment epithelium (RPE) was rapidly decreased, and inflammatory cells were accumulated in the inner retina and subretinal space. These changes may contribute to the loss of capillaries close to the photoreceptor cells and RPE in MNU-treated rats.