Regulation of myosin light chain phosphorylation in the trabecular meshwork: role in aqueous humour outflow facility

Mechanistic basis of Rho GTPase-induced extracellular matrix synthesis in trabecular meshwork cells

“…These studies suggest that agents that increase actin depolymerization and decrease cell-ECM interactions and myosin II phosphorylation within cells of the trabecular pathway increase aqueous humor outflow presumably by causing cellular relaxation and by altering the geometry and stiffness of the outflow pathway tissues and fluid flow through the inner wall of SC (41, 51). Conversely, agents that activate Rho GTPase and myosin II activity, including lysophosphatidic acid (LPA), sphingosine-1-phosphate, TGF-␤ 2 , and endothelin-1, decrease aqueous humor outflow facility concomitant with increased contractile activity of the TM cells, indicating a potential importance of actomyosin organization and the contractile force generated by the actomyosin system in the regulation of aqueous humor drainage (16,33,39,57,63).Organization of the cellular actomyosin-based cytoskeletal network is dynamically regulated under physiological conditions. Extracellular signals serve as inputs to drive changes in cell morphology, cell adhesion, contractile/mechanical properties, and gene expression via actin-myosin cross-bridging and mechanotransduction (17,20,21).…”

Effects of Novel Ethacrynic Acid Derivatives on Human Trabecular Meshwork Cell Shape, Actin Cytoskeletal Organization, and Transcellular Fluid Flow

“…[5][6][7][8][9][10][11][12][13][14] ECA and inhibitors of Rho kinase and Myosin Light Chain Kinase, and cytochalasin D and latrunculin-induced increases in aqueous outflow facility have been shown to correlate well with alterations in cell shape and decreased actin stress fibers and focal adhesions. [5][6][7][8][9][10][11][12][13][14] Therefore, we evaluated the effects of ECA derivatives on TM cell shape, actin cytoskeletal organization, focal adhesions, transcellular fluid flow, and cell viability on a comparative basis with the intention of evaluating their low toxicity and high efficacy as assessed by cell morphological and cytoskeletal responses.…”

“…[5][6][7][8][9][10][11][12][13][14] Ethacrynic acid (ECA), a sulfhydryl reactive diuretic and a Na ϩ /K ϩ /Cl Ϫ co-transporter inhibitor, has been demonstrated to lower IOP in living animals, including humans, and perfusion of ECA in enucleated eyes has been reported to increase aqueous humor outflow facility through the conventional outflow pathway. 15,16) In cultured TM cells, ECA induces changes in cell shape and decreases actin stress fibers and focal adhesions.…”

Rho kinase inhibitors for glaucoma treatment - Review

“…The actomyosin system, composed of the contractile proteins actin and myosin, is responsible for regulating contraction and relaxation in muscle tissues, and this system is present in the TM and JCT/SC. In addition, the contractile and relaxation power of the TM influences aqueous humor outflow in an antagonistic manner (26,31) . Relaxation of the TM relaxes the cellular actomyosin system, resulting in cellular relaxation and/or cell shape alteration, which increases the size of the intercellular spaces, leading to increased aqueous outflow (25,26) .…”