The dendritic cell is the fulcrum that controls the innate and acquired immune response. Dendritic cells have been identified within the anterior uveal tract of the eye, but their function, migration, and heterogeneity have been incompletely characterized. They certainly play a vital role in anterior segment inflammation, i.e. uveitis. We have developed a unique technology, intravital microscopy in the rodent eye, that allows us to identify, quantify, and serially photograph dendritic cells within the iris of a living animal. Using this technology in addition to immunohistology, radiation chimeras, and a variety of standard immunological techniques, we propose to: 1) test the hypotheses that anterior uveal dendritic cells are functionally and phenotypically heterogeneous; 2) use gene array to validate further the hypothesis of heterogeneity as demonstrated at the mRNA level for dendritic cell subsets as well as for mature versus immature dendritic cells; 3) use bone marrow chimeras to test the hypothesis that iris dendritic cells transport antigen to the submandibular lymph node; 4) use in vivo immunohistology with intravital microscopy o test the hypotheses that A) the phenotype of iris dendritic cells changes as a result of local antigen stimulation, B) antigen presentation occurs locally within the iris, and C) dendritic cells bearing antigen exit the iris stroma; and 5) test the hypothesis that a phenotypic change in iris dendritic cells could be therapeutically beneficial in suppressing an immune-mediated uveitis. These studies will clarify the function of the immune system within the eye and may suggest novel therapeutic approaches in the treatment of uveitis.
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