Matrix molecules associated with both regulation of inflammation and pathogenic outcomes associated with the surface of the lens in the eyes of EAU mice

This is the authors' abstract. We don't add key points for this paper.

Immune cells with immunoregulatory properties are recruited to the surface of the lens in the Experimental Autoimmune Uveitis (EAU) mouse and remain linked through resolution of EAU inflammation. Since protein components of the extracellular matrix provide biochemical and mechanical signals that regulate immune cell migration and phenotype, we investigated whether EAU inflammation caused matrix molecules to become associated with the lens surface. We focused on matrix proteins known to influence leukocyte phenotype and behavior, and/or lead to pathological outcomes in uveitis. We found that fibrinogen became associated with the lens capsule surface by the peak of EAU inflammation and increased as inflammation was resolved. Although the matrix protein fibronectin, which supports cell attachment and migration, is a normal component of the lens capsule, we found that it had increased along the capsule surface in EAU. MAGP-1 microfibrils had extended across the anterior and posterior lens capsule surface, and there was de novo association of versican and vitronectin with the anterior capsule surface. Aberrant accumulation of matrix proteins on the lens surface correlated with known pathological outcomes of uveitis in the EAU model including adhesion of the iris to the anterior lens surface which can lead to uveitic glaucoma, and increased rigidity of the lens capsule that could be a cause of cataracts resulting from uveitis. The de novo association of these matrix molecules with the lens capsule in EAU highlights changes to the lens microenvironment that can influence immune cell phenotype and behavior and may account for post-inflammatory complications. • EAU inflammation causes de novo association of matrix molecules on the lens surface. • Immune cells link to and integrate within these fibrinogen/fibronectin matrices. • Immune cells travel along MAGP-1-rich microfibrils extended along the lens surface. • Fibrinogen implicated in the adherence of the iris to the anterior lens capsule. • Increased lens capsule rigidity associated with lens capsule matrix changes in EAU.