TPM2 regulates contractility and biomechanical properties in trabecular meshwork cells.

The contraction-relaxation balance of trabecular meshwork (TM) cells is a critical physiological mechanism regulating aqueous humor outflow resistance. Both hypercontractility and impaired relaxation of TM cells can obstruct aqueous humor outflow. Such pathological changes not only directly compromise outflow function but may also reduce the clinical efficacy of ocular hypotensive therapies. However, the molecular regulatory mechanisms underlying TM cell contractility remain incompletely understood. Based on single-cell RNA sequencing data previously generated by our group, our analyses revealed abnormal expression patterns of tropomyosin family members (TPMs) in major TM cell subpopulations in primates with primary open-angle glaucoma (POAG). This study investigated the effects of TPM2 in TM cells on contractile-related molecular expression and biomechanical properties. The results showed that modulating TPM2 expression levels significantly affected the expression of Actin Alpha Cardiac Muscle 1 (ACTC1), Troponin T2, Cardiac Type (TNNT2), alpha-smooth muscle actin (α-SMA), and F-actin in human TM cells (HTMCs), and simultaneously altered the cellular elastic modulus. Thus, TPM2 may regulate aqueous humor outflow by modulating TM cell contractility, altering cytoskeletal architecture, and inducing changes in biomechanical properties.