Although ocular infections with herpes simplex virus type 1 (HSV-1) are a major cause of human corneal disease and blindness, as yet the mechanisms responsible for the pathological processes seen in association with HSV-1 induced ocular disease are not well-understood. It is thought that the pathology of HSV-1 eye disease is a result of viral factors, immunological factors or a combination of both. An interesting pattern of bilateral disease results after inoculation of HSV-1 into the anterior chamber of one eye of either a mouse or a rabbit. In the injected eye, there is an acute destructive inflammatory reaction in the anterior segment (cornea, anterior chamber) and the anterior portion of the uveal tract (iris and ciliary body) which occurs within three days of virus inoculation. The uninoculated contralateral eye exhibits a delayed destructive reaction which is limited to the posterior segment (vitreous, retina, choroid) and iris of that eye only. The cornea of the uninjected eye is spared while the retina of this eye is destroyed; the cornea and retina of the injected eye show the reverse pattern of destruction. Using a mouse (BALB/c) model, the aims of the research proposed herein are to: (1) define the virological (such as defective interfering particles or interferon) and/or immunological factors responsible for the preservation of the retina of the injected eye; (2) determine whether virus replication alone accounts for the destruction of the retina of the contralateral eye or whether virus-induced immunopathologic processes contribute to the retinitis; (3) determine when and by what route (or routes) the virus leaves the injected eye following anterior chamber inoculation of one eye; (4) discover what role innate susceptibility to HSV-1 plays in ocular disease produced by the anterior chamber inoculation of HSV-1. The goals of this project will be achieved by in situ tissue hybridization techniques using cloned probes from specific regions of the HSV-1 genome to locate the virus after inoculation. These in situ hybridization studies will be complemented by light and electron microscopic examination of tissues from time course experiments. Animals with varying levels of susceptibilities to HSV-1 or with specific immunological defects will be used to allow a better definition of what host factors play a role in the pathogenesis of ocular HSV-1 infections.
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| Cathcart, Heather M; Fields, Mark A; Zheng, Mei et al. (2009) Infiltrating cells and IFNgamma production in the injected eye after uniocular anterior chamber inoculation of HSV-1. Invest Ophthalmol Vis Sci 50:2269-75 |
