Chemokine Gene Expression in Iris-ciliary Body During Experimental Autoimmune Uveoretinitis

Abstract

Abstract: : Purpose: To evaluate, through differential gene expression of chemokines in iris ciliary body (I/CB), the extent to which leukocyte recruitment to the ocular anterior segment participates in the pathogenesis of experimental autoimmune uveoretinitis (EAU) in mice. Methods: B10.A mice were immunized with 50 micrco g of interphotoreceptor retinoid binding protein (IRBP) mixed with complete Freund's adjuvant. Aqueous humor (AqH) was collected at 0, 11, 17, and 28 days and assayed for leukocyte content and protein levels. Enucleated eyes were subjected to histologic analysis. Chemokine gene expression in I/CB was determined at these same time points by a multiprobe ribonuclease protection assay (RPA) system. Results: Inflammation was detected in the anterior chamber (AC) at 11 days and leukocyte recruitment continued thereafter. Polymorphonuclear neutrophils (PMN) were the predominant cell type in the AC, whereas macrophages/monocytes and lymphocytes were predominant in the retina/subretinal space at 17 days. Peak gene expression of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and MIP-2 and interferon-gamma-inducible protein of 10 kd (IP-10) was detected in I/CB on day 11, whereas peak expression of RANTES and eotaxin was observed at 17 days. Conclusions: Early I/CB peak expression of mRNA for MIP-2 followed by PMN recruitment into the AC, suggests that PMN may play an important role in EAU pathogenesis.

Keywords: anterior chamber • cytokines/chemokines • uveitis-clinical/animal model