Infection of retinal neurons during murine cytomegalovirus retinitis

Abstract

Purpose: Previous results suggest that retinal neurons are infected early during murine cytomegalovirus (MCMV) infection of the inner retina. The purposes of this study were to identify which retinal neurons are infected and to determine the routes by which MCMV spreads in the retina.

Methods: Immunosuppressed (IS) BALB/c mice were inoculated with 5 x 10(3) PFU of MCMV (k181) through the supraciliary route. Injected eyes were collected at several times after inoculation, sectioned, and examined by electron microscopy and by staining for retinal cell antigens and for MCMV early (EA) or late (LA) antigen.

Results: MCMV-infected cells were observed in the choroid and RPE by day 3 after infection (PI) and in the inner retina beginning at day 5 PI. At this time, many horizontal and bipolar cells were MCMV-antigen-positive but only rare MCMV-infected amacrine cells (glycine positive or gamma-aminobutyric acid [GABA] positive) or MCMV-infected ganglion cells (NF positive) were observed in the inner retina. At day 10 PI, most virus-infected cells were glial fibrillary acidic protein (GFAP)- and GABA-positive glia. Virions were observed by electron microscopy in the choroid, RPE, and inner nuclear layer of the retina. Although virions were observed in the endothelium of the retinal vessels and the nearby retinal cells, the endothelial cell lining of the retinal vessels remained intact. Both apoptotic cells and necrotic cells were seen in the inner retina.

Conclusions: In the inner retina, horizontal and bipolar cells were the early (< or = day 7 PI) targets of MCMV infection. Virus spread from the RPE and the photoreceptor layer to the inner retina through infected Muller cells and within the inner retina horizontally through infected horizontal cells.