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M. Zhang, H. Xin, S.S. Atherton; Localization of Reactivated MCMV in the Eye Following immunosuppression of Latently MCMV Infected Mice . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1132.
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Purpose: A limited amount of ocular MCMV reactivation is observed after deep systemic immunosuppression (IS). In addition, the extent of MCMV reactivation is increased after systemic IS plus depletion of ocular macrophages by clodronate–liposomes. The aim of this study was to determine in which ocular cells MCMV reactivates. Methods: Four months after inoculation of 5x102 PFU of MCMV k181, latently infected BALB/c mice were divided into 4 groups. Mice in groups 1, 2 and 3 were IS with methylprednisolone and antibodies against T cells. Mice in group 4 were not IS. Seventeen days after systemic IS, the mice in groups 1 and 2 were injected with clodronate–liposomes or PBS–liposomes respectively via the supraciliary route. The mice were sacrificed after 3 weeks of immunosuppression. To identify which retinal cells were infected with MCMV, frozen sections of eyes were double stained with FITC labeled anti–MCMV early antigen (EA) and Texas Red–labeled antibodies (Ab) specific for retinal cells including RPE–65 (RPE cells), GFAP (glial cells), Mac–1 (macrophages/microglia), PKC–α (bipolar cells), Goα (bipolar cells), glycine (amacrine cells), or calbindin (horizontal cells). Results: No MCMV infected cells were detected in the injected eye of control mice (group 4). A few virus–infected cells were observed in the injected eye of mice in group 2 and group 3. Most of the MCMV–infected cells were in the RPE layer, although positive cells were observed occasionally in other sites including the anterior segment, inner retina, and choroid. In contrast, IS plus depletion of ocular macrophages (group 1) resulted in many MCMV–infected cells in all layers of the retina. Double staining indicated that MCMV infected cells in the area of the RPE or in the photoreceptor layer were RPE cells. The majority of virus–infected cells in the inner retina were glia and horizontal cells, a few of which were macrophages/microglia or bipolar cells. Conclusions: The RPE is the initial and major site of MCMV reactivation in the outer retina whereas glia and horizontal cells are sites of MCMV reactivation in the inner retina. These results suggest that in addition to T cells, macrophages play a role in preventing MCMV reactivation in the posterior segment of the eye.
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