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

Authors

Phuong M. Le, Department of Pathology and Genomic Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
JodiRae DeDreu, Department of Pathology and Genomic Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Mary J. Mattapallil, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Rachel R. Caspi, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Ryan Tomlinson, Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA; Department of Oral and Maxillofacial Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Mary Ann Stepp, Department of Anatomy and Cell Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA; Department of Ophthalmology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
A Sue Menko, Department of Pathology and Genomic Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA; Department of Ophthalmology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: sue.menko@jefferson.edu.

Document Type

Journal Article

Publication Date

7-18-2025

Journal

Experimental eye research

Volume

259

DOI

10.1016/j.exer.2025.110529

Keywords

Autoimmune uveitis; Immune cells; Immunoregulatory; Inflammation; Lens; Matrix

Abstract

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.

APA Citation

Le, Phuong M.; DeDreu, JodiRae; Mattapallil, Mary J.; Caspi, Rachel R.; Tomlinson, Ryan; Stepp, Mary Ann; and Menko, A Sue, "Matrix molecules associated with both regulation of inflammation and pathogenic outcomes associated with the surface of the lens in the eyes of EAU mice" (2025). GW Authored Works. Paper 7565.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7565

Department

Anatomy and Regenerative Biology