Apoptosis in the retina during MCMV retinitis in immunosuppressed BALB/c mice.
Cytomegalovirus (CMV) retinitis is the most common opportunistic ocular infection observed in immunosuppressed (IS) adult and pediatric patients. Due to the species restriction of the cytomegaloviruses, mice infected with murine CMV (MCMV) have been used to study the pathogenesis of CMV retinitis. The objectives of this study were to determine if retinal glial cells are the targets of MCMV infection and to determine which cells in the retina become apoptotic following inoculation of MCMV via the supraciliary route. Adult female BALB/c mice were IS with methylprednisolone; one half of the mice were injected with MCMV and one half of the mice were injected with an equivalent volume of tissue culture medium via the supraciliary route. Animals were sacrificed and frozen sections of eyes were stained for MCMV early antigen, RPE65, CD45 or TUNEL; additional slides were double stained with combinations of the above reagents. The results indicate that most apoptotic cells in the retina were not virus infected, most apoptotic cells were not infiltrating CD45 positive leukocytes, and retinal glial cells were infected with MCMV but only late in infection. Together, these results suggest that retinal cells that undergo apoptosis during MCMV infection are neurons and that apoptosis of uninfected bystander cells is an important component of the pathogenesis of CMV retinitis.