Purpose. Apoptosis occurs in JHM virus infected mouse retinas. In order to determine if apoptosis contributes to retinal degeneration, we evaluated the time and dose response of virus infection associated with apoptosis within the retinas of Iwo strains of mice and three virus permissive cell cultures. Methods. In vivo. BALB/c and CD-1 mice were inoculated with coronavirus. JHM strain, or media by the intravitreal route. In vitro, mouse macrophages, liver cells, and L2 cells were infected with JHM virus. At varying times after inoculation, mouse retinas and cells were assayed by terminal deoxynucleotidyl transferase conjugated-dUTP nick end labeling (TUNEL), double-staining. DNA laddering and electron microscopy (EM) to detect apoptosis. Results. Virus infection in BALB/c and CD-1 mice resulted in widespread apoptosis within the retina during the acute phase of the disease (day 1-10). Feu apoptotic cells were observed after 20 days, when infectious virus was absent and viral RNA persisted. Double-staining and EM demonstrated that the apoptotic cells were not macrophages, the predominant infiltrating cell, but rather resident retina cells within the outer nuclear layer. This finding correlated apoptosis with acute infection in a mouse strain that was retinal degeneration susceptible (BALB/c) and in a mouse strain that was retinal degeneration resistant (CD-1 ). Temporally related to retinal apoptosis was the presence of CDS+ T cells and the cytokine. TNF-a. both of which trigger apoptotic events. In vitro studies demonstrated that the munne coronavirus. JHM strain, did not induce apoptosis directly. This inability to induce apoptosis may correlate with the viruses ability to persist within the host. Conclusions. Retinal apoptosis appears to be an indirect result of coronavirus infection and is likely to reflect host mechanisms of virus-elimination within the retina. Furthermore, in this model system, induction of retinal apoptosis is insufficient, by itself, to trigger retinal degeneration.
|Original language||English (US)|
|Journal||Investigative Ophthalmology and Visual Science|
|Publication status||Published - 1997|
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