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Abstract
PURPOSE: To establish the presence of distinct populations of macrophages and MHC class II (Ia)-positive dendritic cells (DC) in the iris and ciliary body of the rat, mouse, and human eye. METHODS: Iris-ciliary body wholemounts from a variety of rat strains, balb/c mice, and human eyes were investigated by single and double immunohistochemistry, immunoelectron microscopy, and confocal microscopy to determine the phenotype, density, distribution, and location of macrophage and DC populations. RESULTS: Dendritiform and pleiomorphic macrophages were distributed in a regular array within the rat iris and ciliary body stroma (600 to 700 cells/mm2 or 7000 cells per iris). Ia+ DC were distributed in a similar regular network (400 cells/mm2 or 5500 cells per iris) within the iris stroma and ciliary epithelium. In the rat, a strain-dependent variation in the numbers of DC was noted, F344 rats displaying highest numbers of DC (962 +/- 398 cells/mm2) and WAG strain the lowest numbers (285 +/- 218 cells/mm2). Double color immunoperoxidase staining using anti-Ia and anti-pan specific macrophage monoclonal antibodies revealed that macrophages and Ia+ DC are distinct populations with only 5% to 15% overlap. Single immunoperoxidase of mouse iris and ciliary body using anti-pan macrophage and anti-Ia antibodies produced findings identical to those in rat. Preliminary studies of human tissue using confocal microscopy of immunostained whole irides also revealed a regular array of macrophages and MHC class II (HLA-DR)+ dendritiform cells. CONCLUSIONS: The mammalian iris contains rich networks of dendritiform-pleiomorphic macrophages and MHC class II+ DC. These findings suggest that the DC in the tissues lining the anterior chamber represent a rich network of putative antigen presenting cells and are the most likely candidates for transmitting antigen-specific signals from the anterior chamber in vivo and in experimental models such as ACAID: These observations have wide implications for the understanding of the pathogenesis of anterior and posterior uveitis.