Abstract: The structural and functional abnormalities of trabecular meshwork increase resistance to drainage of aqueous humor in primary open-angle glaucoma (POAG), resulting in pathologically high intraocular pressure. Trabecular meshwork reshape the cytoskeleton and form cross-linked act in network under transforming growth factor (TGF)-β-mediated Rho-GTPase pathway. Extracellular matrix accumulates and forms crosslinking through TGF-β-mediated Smad nuclear pathway and non-classical Smad pathway. Cell-matrix interaction increases the hardness and decreases the compliance of the trabecular meshwork. Cell aging and autophagy dysfunction activate apoptosis through exogenously and endogenously reactive oxygen species (ROS) attack. This review will discuss the interaction between trabecular meshwork and the microenvironment, providing further information to explore pathogenesis of POAG. (Int Rev Ophthalmol, 2022, 46:  150-16)

Key words: primary open-angle glaucoma, cytoskeleton dysfunction, extracellular matrix