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H. M. Cathcart, M. Zheng, Y. Liu, B. Marshall, S. S. Atherton; Interferon-Gamma, Macrophage Depletion and Intraocular Spread of HSV-1 After Anterior Chamber Injection. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2644.
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Following uniocular anterior chamber (AC) inoculation of HSV-1, the anterior segment of normal BALB/c mice becomes inflamed and infected, and HSV-1+, interferon gamma (IFNγ)+ and Mac-1+ cells are observed in the anterior segment of the injected eye through day 5 post injection (p.i.). However, in these mice, virus does not spread from the anterior segment to infect the central retina of the injected eye. The aim of this study was to determine whether loss of IFNγ or depletion of macrophages would affect the timing and/or pattern of virus spread in the injected eye.
Female, IFNγ-/- or macrophage depleted BALB/c mice were injected in one AC with 3 x 104 PFU of HSV-1 (KOS) in a volume of 2µl. Mice were depleted of macrophages locally (eye) and systemically (spleen) by injecting clodronate encapsulated liposomes into the subconjunctiva (30µl) and intravenously (150 µl) through the tail vein. Following virus injection, mice were sacrificed at 24, 48, 72 and 120 hrs p.i., the eyes were enucleated, prepared for flow cytometry and stained with antibodies specific for Mac-1 (CD11b) or F4/80; frozen sections of other eyes were stained with an antibody specific for HSV-1.
IFNγ-/- mice survived through day 5 and macrophage depleted mice survived through day 3 following AC injection of HSV-1. In clodronate treated mice, the number of Mac-1+ and F4/80+ cells was significantly reduced in the injected eye and spleen compared with mock depleted mice. Although the timing of virus spread in the injected eye was similar in IFNγ-/- mice compared with control mice and also in clodronate depleted mice compared with mock depleted mice, in the IFNγ-/- and clodronate depleted animals, the extent of infection in the anterior segment was greater, more of the retina, including the central retina, was infected, and virus infection of the ganglion cell layer was observed in these mice.
Taken together, these results suggest that IFNγ and macrophages may be important not only in limiting virus spread from the anterior segment to the posterior segment but also in preventing virus spread within the retina early after AC inoculation of HSV-1.
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