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John E. Bigger, Minoru Tanigawa, Ming Zhang, Sally S. Atherton; Murine Cytomegalovirus Infection Causes Apoptosis of Uninfected Retinal Cells. Invest. Ophthalmol. Vis. Sci. 2000;41(8):2248-2254.
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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
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
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