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Deborah Lipski, Remi Dewispelaere, Ariane Frère, Laure E Caspers, Catherine Bruyns, François Willermain, Ophthalmology Group; Characterization of Retinal Expression of Intercellular Adhesion Molecule 1 (ICAM-1) During Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5306.
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During inflammation, activated T cells producing pro-inflammatory cytokines induce the expression of adhesion molecules, which allow for the recruitment of immune cells responsible for tissue damage. Immunoglobulin superfamily members play a central role in leukocyte adhesion to the blood-retinal barrier (BRB). We have previously demonstrated that VCAM-1 is induced on BRB cells during experimental autoimmune uveitis (EAU) in correlation with the severity of the disease. Here, we investigate the retinal expression of ICAM-1 in EAU and the expression of integrins VLA-4 and LFA-1, respectively VCAM-1 and ICAM-1 ligands, on transferred uveitogenic cells.
C57Bl/6 mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) peptide 1-20. After 12 days, T cells were semi-purified from draining lymph nodes and spleens, restimulated in vitro with IRBP1-20 for 2 days and injected to C57Bl/6 mice. Before being adoptively transferred, T cells were tested by flow cytometry for their expression of CD4, VLA-4 and LFA-1. Fundoscopy was performed before euthanasia after 1, 2 or 3 weeks. Eyes were processed and ICAM-1 expression analyzed by immunohistology. Co-labellings for GFAP and endoglin detection were done to identify cells expressing ICAM-1.
ICAM-1 is faintly present in naive eyes but its expression develops in parallel to EAU, with an intensity and extension correlated to disease severity. ICAM-1 expression is maximal at the retinal pigment epithelium level but it also extends to the ciliary body, the external limiting membrane, the inflammatory cells infiltrating the retina and the vitreous and the vascular endothelial cells in vasculitis lesions. VLA-4 and LFA-1 are expressed on both T and non T cells, VLA-4 sparsely and LFA-1 ubiquitously.
This work provides the first full description of ICAM-1 expression in the retina during EAU and the first study of VLA-4 and LFA-1 membrane expression on uveitogenic cells. As previously shown for VCAM-1, ICAM-1 expression develops simultaneously with uveitis and correlates with the severity of the disease. However, VCAM-1 and ICAM-1 have a distinct intraocular distribution. VCAM-1 seems most strongly expressed on the internal BRB while ICAM-1 predominates on the external BRB. ICAM-1 and VCAM-1 may thus represent differential entry pathways for inflammatory cells during EAU.
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