Murine cytomegalovirus infection causes apoptosis of uninfected retinal cells.

PURPOSE To determine the role of apoptosis in prevention and/or exacerbation of retinal disease in a mouse model of cytomegalovirus retinitis. METHODS Immunocompetent or T-cell- depleted BALB/c mice were injected with murine cytomegalovirus (MCMV) by supraciliary injection. On sequential days after infection, mice were killed, and eyes were harvested for cryosectioning or for DNA extraction. Ocular sections were stained with monoclonal antibodies specific for MCMV or for T cells or used in the TdT-dUTP terminal nick-end labeling (TUNEL) assay to detect apoptotic cells. RESULTS In immunocompetent BALB/c mice, TUNEL assays revealed that a large area of the retina was apoptotic in relation to the relatively small number of MCMV-infected cells that were observed in the subjacent choroid and/or retinal pigment epithelium. In infected eyes from T-cell- depleted mice, there were more TUNEL-positive cells, and the areas of apoptosis were more extensive than in immunocompetent mice. These observations correlated with the increased extent of MCMV infection that is observed in the eyes of T-cell- depleted mice. However, irrespective of immune status, TUNEL-positive apoptotic cells were present mainly in areas of the retina overlying areas of MCMV-infected choroid and/or retinal pigment epithelium. More intense DNA laddering, indicative of increased apoptosis, was observed in the posterior segments of the eyes of T-cell- depleted mice after supraciliary inoculation with murine cytomegalovirus compared with less intense DNA laddering in the posterior segments of eyes of immunocompetent MCMV-infected mice. CONCLUSIONS The ability of the mouse's immune system to control MCMV infections in some tissues depends on induction of apoptosis in virus-infected cells. However, in the retina, cells undergoing apoptosis were not virus-infected, a finding that suggests that apoptosis of uninfected retinal cells may play a role in the pathogenesis of MCMV retinitis.