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Yun Wang, Barbara Detrick, Zu-Xi Yu, Jun Zhang, Laura Chesky, John J. Hooks; The Role of Apoptosis within the Retina of Coronavirus-Infected Mice. Invest. Ophthalmol. Vis. Sci. 2000;41(10):3011-3018.
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purpose. To evaluate the possible roles of apoptosis in the murine retinopathy
induced by coronavirus.
methods. Mice were inoculated with virus intravitreally. Mouse eyes harvested at
varying times after inoculation were evaluated for apoptotic and
immunologic events by hematoxylin and eosin staining,
immunohistochemical staining, in situ terminal
deoxynucleotidyltransferase dUTP nick-end labeling (TUNEL) assay, and
electron microscopy. Isolated retinas were analyzed for infectious
virus and for expression of apoptosis-associated genes.
results. The number of apoptotic events was significantly elevated in infected
eyes from BALB/c and CD-1 mouse strains, reaching a maximum at days 6
through 10, and returning to normal levels at day 20. The majority of
apoptotic cells were observed in the outer nuclear layer of the
infected retina. In contrast, few apoptotic cells were observed in
normal or mock-injected mouse eyes. Apoptotic events within the retina
were associated with the presence of viral antigen, infiltration of
CD8+ T cells, and clearance of infectious virus. Reverse
transcription–polymerase chain reaction (RT-PCR) analysis identified
the upregulation of Fas ligand (FasL) and granzyme B mRNAs within the
infected retinas. The development of apoptosis, regulative gene
expression, and viral clearance were similar in both retinal
degeneration–susceptible (BALB/c) and –resistant (CD-1) mice.
conclusions. Retinal apoptosis was associated with retinal inflammation, a decrease
in infectious virus, and upregulation of genes associated with CTL
killing. These studies indicate that retinal apoptosis may be one of
the host mechanisms that contribute to limiting this retinal
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