The Monocyte Chemokine Receptor Cx3Cr1 Does Not Play a Significant Role in the Pathogenesis of Experimental Autoimmune Uveoretinitis

Abstract

PURPOSE. To examine the role of the monocyte chemokine receptor CX3CR1 in experimental autoimmune uveoretinitis (EAU).METHODS. EAU was induced in naive WT, Cx3cr1gfp/+, andCx3cr1gfp/gfp C57Bl/6 mice or chimeric mice. Ocular disease severity was graded by histologic analysis of resin sections. In addition, immunohistochemistry and confocal microscopy were performed on retinal whole mounts to characterize the monocytic infiltrate and changes in retinal microglia. To determine the relative roles of resident and blood-borne monocytederived cells in the active phase of uveoretinitis, EAU was induced 4 weeks after transplantation in chimeric mice (Cx3cr1gfp/gfp3WT and Cx3cr1gfp/+3WT), and analysis was performed at days 14, 16, 21, and 28 after immunization. RESULTS. After EAU induction, disease scores were not significantly different in WT, Cx3cr1gfp/+, and Cx3cr1gfp/gfp mice. Chimeric studies revealed both donor- and host-derived monocyte- derived cells in the inner retinal layers during early EAU; however, it was donor monocytic cells that infiltrated the photoreceptors, the site of the target antigen. The absence of CX3CR1 did not impede the ability of monocyte-derived cells from Cx3cr1gfp/gfp donor mice to infiltrate during the peak of EAU. CONCLUSIONS. The lack of CX3CR1 on monocyte-derived cells does not significantly influence the onset or severity of EAU. In addition, chimeric studies revealed that it is primarily bloodderived monocytes that mediate photoreceptor damage in the effector pha. © Association for Research in Vision and Ophthalmology.