The pathogenesis of ocular disease induced by herpes simplex virus Type 1 is poorly understood, in part because of difficulty in differentiating between immune- and virus-mediated cytopathic effects occurring at the site of ocular infection. We have developed a murine model of ocular herpes infection in which a distinctive pathologic process occurs following intracameral inoculation of HSV-1: virus-injected eyes exhibit a severe keratouveitis while the posterior segments remain relatively normal except for a minimal inflammatory infiltrate in the ganglion cell layer. In marked contrast, contralateral uninjected eyes develop primarily posterior segment disease in which an intense inflammatory reaction leads to total retinal necrosis within two weeks. Of note is the fact that both retinas are preserved following bilateral inoculation of HSV-1. These differential pathologic features can be used to advantage in studies on the effects of manipulation of systemic immune responses on ocular disease. The model will permit in vitro and in vivo studies designed to: (1) differentiate between immune-mediated and virus-mediated mechanisms involved in the disease pathogenesis; (2) determine the local immune elements (lymphoid subpopulations, antibody, lymphokines) and their function at the site of the pathologic lesion: and (3) determine the relationship of intraocular immune responses to systemic immune responses induced by intracameral inoculation of virus. Intracameral presentation of HSV-1 to mice induces anterior chamber associated immune deviation (ACAID), in which anti-HSV T cell-mediated responses are suppressed while humoral responses are normal. Alterations in the course of ocular disease following depletion or reconstitution of specific lymphoid populations will enable us to determine their role(s) in hepatic ocular disease, as well as which aspects of systemic immune deviation influence the ocular disease. These studies will contribute also to differentiation between nonspecific inflammatory and specific immune-mediated effector mechanisms which occur in the eye during ocular infections. Ocular herpes infections pose important clinical problems. Understanding the relationship of local and systemic immune responses to the disease pathogenensis may aid in the development of more effective therapeutic measures, not only for herpetic ocular disease, but for other ocular disorders as well.
