MACROPHAGE SUBPOPULATIONS AND RPE ELIMINATION IN THE PATHOGENESIS OF EXPERIMENTAL AUTOIMMUNE PIGMENT EPITHELIAL PROTEIN-INDUCED UVEITIS (EAPU)

Experimental autoimmune pigment epithelial protein-induced uveitis (EA PU) is a new type of disease that destroys the retinal pigment epithel ium (RPE), and exhibits a hitherto unknown form of progressive chorior etinal dystrophy in which neuroretinal inflammatory foci are absent. T he present study was aimed at studying the expression of adhesion mole cules, and the kinetics of the appearance of the main types of macroph ages and other intraocular immunocompetent cell populations in the var ious stages of this disease. EAPU was evoked in Lewis rats by immuniza tion with the membrane protein from bovine RPE cells containing PEP-65 as main constituent. In the uvea, increased expression of intercellul ar adhesion molecule-1, of class II major histocompatibility complex a ntigen, and of ED2 macrophage reactivity were observed closely before the onset of EAPU. Expression of these reactivities was also slightly elevated by injections of the applied adjuvants alone. The onset of EA PU was mainly characterized by initial uveal infiltrations of ED1+ mac rophages and a minor population of CD4 T cells, and an increase in ED3 , ED7 and perivascular ED2 reactive macrophages. This was followed by the development of focal accumulations of ED1+ cells at both sides of the Bruch's membrane-RPE layer (Dalen-Fuchs nodules) which was permeat ed and disintegrated at these sites. The outer choroidal layer, the an terior iridal surface, and the base of the ciliary body more frequentl y contained active inflammatory cells than the other uveal areas. Lymp hoid cells were found scattered through the uvea, aqueous and vitreous . The sites of increased activity of ED2+ and ED3+ cells in the uvea w ere rather similar to those of ED1 macrophages in the various stages o f EAPU. Starting from multiple foci, the process of the formation of p laque-shaped cell accumulations in severe EAPU progressed along the RP E and exhibited a chronic character. The results of this study show th at ED1+, ED2+, ED3+ and ED7+ subpopulations of macrophages are activel y involved in an immunopathological process in which the RPE is the ta rget. The thickening of the plaque-shaped cell accumulations stops if the integrity of all RPE cells at that site has been affected. We post ulate that this is the result of antigen elimination while additional influence of the abrogation of RPE cytokine production is presumed. (C ) 1996 Academic Press Limited