Resident and infiltrating cells in the rat iris during the early stages of experimental melanin protein-induced uveitis (EMIU)

Experimental melanin protein-induced uveitis (EMIU) is reported to be a model of anterior uveitis and choroiditis in which the retina is spared. In this study, we chose to compare EMIU with experimental autoimmune uveoretinitis (EAU), a well-recognised model of endogenous posterior uveitis, with regard to the nature and dynamics of the cellular infiltrate in the iris. Female Lewis albino rats were immunised with mixtures of crude retinal extract/complete Freund's adjuvant (CFA) (EAU), phosphate-buffered saline/CFA (controls), or iris melanin/CFA (EMIU) using established protocols. Animals were sacrificed on days 10 and 13 (around disease onset). Following whole body perfusion fixation, irides were dissected from the remainder of the globe. Iris wholemount preparations were then subjected to immunohistochemical analysis in order to investigate both the dynamics of infiltrating leukocytes and the effects of the inflammatory changes on resident immune in the iris. The nature of the cellular infiltrate in both EMIU and EAU models was essentially similar, namely there was a rich infiltrate of EDI mononuclear cells, Ox42 neutrophils and T cells. Resident tissue macrophages (ED2) were slightly below normal densities in the iris of EAU animals and marginally elevated in EMIU animals. MHC class II (Ia) staining, associated in the nonnal eye with dendritic cells (Dc), was considerably elevated in EMIU. It is likely that this was due to both increased Dc numbers and an influx of Ia exudate macrophages. No striking difference was found in the nature and phenotype of the cellular infiltrate in the iris at the onset of the disease in these two models of uveitis (EAU and EMIU). This suggests that the anterior segment inflammation in both models represents non-specific changes secondary to cytokine release associated with interaction of activated antigen-specific T cells and target antigens, namely retinal photoreceptors in EAU and uveal tract melanin-containing cells in EMIU. Alternatively, it may suggest that antigen-presenting cells resident in the iris and ciliary body in normal eyes have access to ocular antigens on both sides of the blood-ocular barrier and are capable of activating circulating antigen-specific T cells in these models.