In an Experimental Autoimmune Uveitis Model, Immune Cells Populate the Lens Surface-Associated Ciliary Zonules and Transit the Lens Capsule

Abstract

Purpose : In this study we addressed the question whether, in inflammatory/autoimmune diseases like uveitis, immune cells associate with the ciliary zonules extended along the lens capsule surface and migrate across the capsule where they could cause lens opacities.

Methods : Experimental Autoimmune Uveitis (EAU) was induced by immunizing C57BL/6J mice with a uveitogenic epitope of the interphotoreceptor retinoid binding protein (hIRBP651-670). Eyes were processed 14, 19, and 26 days after immunization and examined by SEM or by confocal imaging for localization of immune cells using antibodies to CD45, b2 integrin, CD68, GR-1, and CD3.

Results : Labeling of ocular sections with immune cell markers showed that inflammation due to autoimmune uveitis leads to the association of immune cells with the anterior, equatorial, and posterior surfaces of the lens capsule at D14 post-injection with hIRBP peptide. The immune cells detected at D14 included macrophages, leukocytes, and B cells. Immune cell types remain associated with the lens surface at D19 and D26 post-immunization. We also observed that immune cells were moving into the lens capsule by D19. SEM analysis of whole lenses revealed that the infiltration of immune cells on the lens surface is extensive with most of these cells localized within zonule fibrils, giving them an appearance similar to neutrophil NETs. Clusters of immune cells present on the anterior and posterior surface often had rounded morphology. Other morphologies were seen on the lens anterior surface including immune cells with a concave morphology (non-RBC) that appeared to be burrowing into the lens capsule. By D26, when the acute inflammation in the EAU model was largely resolved, immune cells remained localized within the ciliary zonules along the lens surface.

Conclusions : In the autoimmune disease uveitis, immune cells of various types infiltrate into the ciliary zonules along the anterior and posterior surfaces of the lens and migrate into the matrix of the lens capsule. These immune cells have the potential to become the myofibroblasts associated with cataracts and Posterior Capsular Opacification.

This is a 2020 ARVO Annual Meeting abstract.