The present proposal is aimed at a study of the hypothesis that the in situ formation of immune complexes within the anterior segment may be the cause of acute and chronic anterior segment inflammation through the activation of the complement cascade, influxes of inflammatory cells and resulting tissue damage. We further postulate that antigens involved in in situ anterior segment immune complex formation may have diverse origins, as has been most clearly demonstrated for similar complexes in the kidney. A first group comprises autoantigens intrinsic to anterior segment structures, such as laminin, fibronectin and collagen. A second group composed of extrinsic antigens may enter the anterior segment by vasopermeability leakage and bind non-immunologically to various structures therein. This extrinsic group includes both autoantigens derived from other body tissues as well as antigens of invading bacteria and viruses. Humoral immune responses to antigens of both groups will result in the local presence of specific antibodies and, eventually, in the formation of in situ immune complexes. This may be the initiating or perpetuating mechanism of a variety of clinically important anterior segment disorders, among which uveitis, glaucoma and hypotony are the prime focus of this proposal. This project specifically aims to develop two models of endocular inflammation. The first model is based on the reaction between an autoantigen endogenous to the anterior segment, laminin, and its homologous antibody, that will be passively transferred by repeated intracameral injections of feline eyes. The resulting immune complexes will bind complement and thereby result in inflammatory changes within the anterior segment. The second model is caused by immune reactions to an exogenous antigen, Concanavalin A, normally not present within the anterior segment, but that after intracameral injection binds in a long-lasting fashion to defined carbohydrate components of cell membranes and connective tissue. Various immunological mechanisms, including in situ formation of immune complexes, may be involved in the pathogenesis of lectin-induced endocular inflammation. In both models, the induction of endocular inflammation will be evaluated in vivo by serial clinical biomicroscopic observations, changes of intraocular pressure, vasopermeability and aqueous flow rate, correlated with in vitro immunological, immunohistochemical and histopathological studies.
