Matrix stiffness regulates traction forces, cytoskeletal dynamics, and collagen reorganization in trabecular meshwork cells in glaucoma

Abstract

Increased adhesion forces between trabecular meshwork (TM) cells and the extracellular matrix (ECM) in the human outflow pathway are associated with elevated intraocular pressure (IOP), a key risk factor for primary open-angle glaucoma (POAG). This study examines how matrix stiffness affects traction forces and collagen fibril organization in normal and glaucomatous TM cells using collagen gels with stiffness levels of 4.7 and 27.7 kPa. Normal high-flow (HF) TM/juxtacanalicular tissue (JCT) cells showed greater traction forces on the stiffer gels, whereas glaucomatous HF TM/JCT cells generated greater forces on the softer gels. These differences correlated with findings that normal cells are ∼1.6-fold stiffer than their glaucomatous counterparts. Glaucomatous cells also exhibited anisotropic collagen fibril alignment and distinct cytoskeletal dynamics. These results suggest that altered mechanosensitivity and ECM reorganization in glaucomatous TM cells may contribute to promoting ECM stiffening, elevated IOP, and disease progression, highlighting potential therapeutic strategies.