Integrin β1 mediates mechanosensitive regulation of human trabecular meshwork cell functions in response to substrate stiffness

Increased extracellular matrix (ECM) stiffness is a well-recognized pathological hallmark of the trabecular meshwork (TM) in glaucomatous eyes; however, the mechanotransductive pathways by which TM cells sense and respond to mechanical cues remain incompletely understood. In this study, we identified integrin β1 as a key stiffness-responsive molecule, with its fluorescence signal and membrane localization significantly enhanced in human trabecular meshwork cells (hTMCs) cultured on stiffer substrates. Functional blockade of integrin β1 led to a marked reduction in cell proliferation, migration, and phagocytic activity across all stiffness conditions. Notably, the magnitude of blocking effects varied with substrate stiffness: inhibition of proliferative and migratory capacities was more pronounced on rigid substrates, whereas blockade-induced reduction in phagocytic activity was more evident on compliant substrates. These findings suggest that integrin β1 plays a central role in mediating hTMCs responses to biomechanical signals and may contribute to the functional impairment of the TM outflow pathway in the pathogenesis of glaucoma. • Integrin β1 mediates TM cell mechanosensing and response to substrate stiffness • Elevated substrate stiffness significantly reduces TM cell phagocytic capacity • Integrin β1 inhibition markedly attenuates stiffness-dependent TM cell functions