Characterization of retinal expression of vascular cell adhesion molecule (VCAM-1) during experimental autoimmune uveitis

Abstract

Leukocyte adhesion to the blood retinal barrier is a critical step in the pathogenesis of non-infectious uveitis and is mediated in part through the induction of adhesion molecules on retinal cells. Here, we have investigated the retinal expression of Vascular Cell Adhesion Molecule 1 (VCAM-1) in mouse experimental models of non-infectious uveitis. For each eyes, a histological score was given, and the expression of VCAM-1 analyzed by immunohistology. Co-labellings for GFAP, endoglin, aquaporin 4 and recoverin were also performed in order to determine which cell type expressed VCAM-1. In low grade uveitis, obtained after adoptive transfer of semi-purified autoreactive lymphocytes, VCAM-1 was only punctually expressed in the internal limiting membrane and epithelial cells of the ciliary body. Using the same adoptive transfer protocol, we found that, in correlation with disease severity, the staining extended to all internal limiting membranes, vasculitis lesions, Müller cell extensions, outer limiting membranes and RPE cells. VCAM-1 expression in the inner limiting membrane and Müller cell extensions co-stained with GFAP expression. In vasculitis lesions, VCAM-1 co-localized with either GFAP and endoglin expression. The labeling in the outer limiting membrane, did not exactly co-stained with AQ4 (Müller cells marker) or recoverin (photoreceptor marker) and the nature of this expression remained unexplained. Finally, VCAM-1 expression was also analyzed in classical experimental autoimmune uveitis eyes, and a similar pattern of expression was found. In conclusion VCAM-1 is expressed on all blood retinal barrier cells during experimental non-infectious uveitis and might thus play an important role in inflammatory cell recruitment during disease development.