Cellular and molecular mechanisms involved in T cell-mediated autoimmunity affecting the retina are being studied in animal models of experimental autoimmune uveoretinitis (EAU). The questions are aimed at elucidating the mechanisms governing normal development and maintenance, as well as the pathological breakdown, of self-tolerance to retinal antigens. The goal of these studies is to identify the immunogenetic factors predisposing to uveitic disease, learn about the pathogenic mechanisms involved, characterize the immunoreactive cells and their mediators, and finally to use this knowledge for designing novel and rational approaches to immunotherapy. The experimental approaches use rats and mice in which EAU is induced by immunization with retina-derived antigens or with synthetic peptides representing fragments of these antigens. The immunological responses to these antigens are studied at the cellular and molecular levels. Various methods of modulating the immune response to retinal antigens are evaluated for their ability to prevent, cure, or alter the course of the disease. The results help to dissect the immunopathogenic mechanisms involved in EAU to develop immunotherapeutic approaches. One such approach is oral administration of the inciting antigen or its fragments to induce protective immunological tolerance. Genetically altered (transgenic or """"""""knockout"""""""") mice are used to evaluate the role of various components of the immune system in the immunopathogenesis and regulation of uveitis. In vivo functional T cell lines and clones are being developed from lymphoid organs of rats and mice immunized with uveitogenic ocular antigens. The functional properties and specific receptors of these cells are being studied with the purpose of developing strategies for in vivo targeting of the autoimmune cells. To dissect the genetic mechanisms that predispose to uveitis, susceptibility to disease induction and the associated immunological responses are being evaluated in various rodent strains of defined genetic characteristics. Also, EAU in rats and mice serves as a template for the preclinical evaluation of new drugs and compounds as to their effects on the various stages of immunopathogenesis and final disease expression.
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