Cell Motility Dynamics in Glaucoma: Mechanisms, Pathogenic Roles, and Therapeutic Targeting

Cell motility—the dynamic process encompassing migration, adhesion modulation, cytoskeletal remodeling, and extracellular matrix (ECM) interactions—is fundamental to ocular homeostasis. In glaucoma, disrupted motility of trabecular meshwork (TM) and Schlemm’s canal (SC) cells contributes to impaired aqueous humor outflow and elevated intraocular pressure (IOP), while reactive motility of optic nerve head (ONH) glial cells promotes fibrosis and neurodegeneration. Mechanistically, TM/SC motility is regulated by Rho GTPase and ROCK signaling, focal adhesion dynamics, and ECM interactions, while glial cells respond to mechanical stress and cytokines such as TGF-β2. Cytoskeletal alterations, ECM stiffening, and endothelial–mesenchymal transition (EndMT) contribute to glaucomatous damage by reducing normal cell motility and tissue remodeling capacity. Aberrant motility at the ONH, including heterogeneous astrocytic reactivity, leads to lamina cribrosa remodeling and retinal ganglion cell degeneration. Therapeutically, ROCK inhibitors improve TM/SC motility and outflow, suppress EndMT, and may confer neuroprotection. Stem cell–based strategies and modulation of TGF-β2 or mechanotransduction pathways represent emerging approaches to restore physiological motility and regenerative potential. Despite promising advances, challenges remain in ensuring targeted, durable, and safe modulation of cellular dynamics. Understanding and therapeutically harnessing cell motility offers a unifying framework to address both pressure-dependent and neurodegenerative mechanisms in glaucoma.