The induction and immunomodulation of experimental autoimmune uveoretinitis
Experimental Autoimmune Uveoretinitis (EAU), is a T cell mediated disease used as a model for several human inflammatory conditions affecting the posterior segment of the eye, which are immune mediated or autoimmune in nature. In this study an improved method of Interphotoreceptor Retinol Binding Protein (IRBP) preparation was devised (liquid chromatography), in order to establish the poorly characterised Lewis rat model of IRBP induced EAU. The progress of ocular inflammation induced by IRBP was investigated, both histologically (resin embedded, H &'38 E stained) and immunohistologically with particular reference to cells of the mononuclear phagocyte system. CD4&'43 lymphocytes out numbered CD8&43 lymphocytes in early focal lesions of the uvea and sites of retinal perivascular and ciliary body infiltration. A dominance reversed during disease resolution. Macrophages were also prominent throughout EAU: ED2 tissue macrophages in early retinal lesions; a prolonged presence of CD11b/CD18 mononuclear cells in the choroid and retina and early 'mass migration' into the photoreceptor region; and ED3 inflammatory macrophages in the vitreous and photoreceptor region during the late phase of disease. Once characterised this model of EAU was manipulated in vivo by the immunosuppressant macrolides Cyclosporin A, FK-506 and Rapamycin. In order to elucidate the key initiatory mechanisms responsible for the disease state the effects of immunosuppression on antibody production and in vitro cellular responses to antigen/mitogen were investigated.