The long term objectives of this study are to determine the pathogenesis of macular disease associated with ocular histoplasmosis. We will continue to study a primate model developed in our laboratory. Since thousands of Americans are blinded each year by ocular histoplasmosis (OHS), determination of its pathogenesis could lead to substantial improvements in therapy. We have already determined that acute multifocal histoplasmic choroiditis in primates occurs with gradual resolution of active lesions into typical histo scars, retinal pigment epithelial defects, sub-clinical, and """"""""disappearing"""""""" lesions. There is a persistence of chronic inflammation in the choroid for years after the infection (no viable organisms are present). We have recently demonstrated subretinal neovascularization two years after the acute choroiditis, the first time this has been described in a primate model. Following intracarotid challenge with killed H. capsulatum, we have also observed apparent """"""""reactivation"""""""" of choroiditis in some animals. We plan to evaluate this phenomenon in more detail in the current granting period. Our proposed goals are to (1) complete the natural history studies of OHS in primates, (2) detect the antigen which drives the persistent choroiditis by immunofluorescent studies using polyclonal rabbit anti-H. capsulatum antisera, and (3) characterize the immunopathology of reactivation by comparing inflammatory cell types in choroidal lesions before and after antigen challenge using immunocytochemical (monoclonal antibody) techniques to identify helper/inducer T-cells, suppressor/cytotoxic T-cells, B-cells, and macrophages. This study will provide insight into the reactivation response and provide leads to methods to modify this response therapeutically. Ultimately, we feel this study will have direct clinical relevance to the understanding of OHS and its therapy. This is a collaborative study in which the immunocytochemical procedures proposed will be carried out in a modern immunopathology laboratory by fully experienced personnel under the direction of a qualified immunologist.
