ArticleAmerican journal of physiology. Cell physiology2021
TRPV4-Rho signaling drives cytoskeletal and focal adhesion remodeling in trabecular meshwork cells.
Article in American journal of physiology. Cell physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 74 citations in OpenAlex.
- Mechano-immunomodulatory biomaterials: From immune mechanosensing to translational design.Bioactive materials · 2026Review
- TRPV4 regulates intraocular pressure through trabecular meshwork contractility and fibrosis.Channels (Austin, Tex.) · 2026Review
- Investigating the coupled effects of stiffness and stretch on the trabecular meshwork cells using a hydrogel-integrated microfluidic system.Biomaterials science · 2026Article
- Adaptable sliding hydrogels enable pericellular pocket formation while enhancing MSC chondrogenesis and survival in 3D.Bioactive materials · 2026Article
- Orai1 is required for CabioRxiv : the preprint server for biology · 2026Article
- Intraocular pressure induced blood retinal barrier compromise in mouse models and human glaucoma.Nature communications · 2026Article
- Compressive stress-driven Piezo1 activation and Rho-ROCK mechanotransduction promote tumor progression via epigenetic mechanical memory.Science advances · 2026Article
- Pro-Homeostatic Effects of Estrogen on Intraocular Pressure and the Trabecular Meshwork.Investigative ophthalmology & visual science · 2026Article
- Mechanical regulation of metabolism, epigenetics, and their interplay.npj biomedical innovations · 2026Review
- Characterization of the Functional Transient Receptor Potential Vanilloid Channels 1 to 4 in Human Corneal Endothelial Cells.Investigative ophthalmology & visual science · 2026Article
- LIM domain-containing proteins Zyxin and LPP localize to apical epithelial cell-cell junctions at regions of stable F-actin.microPublication biology · 2026Article
- Integrating Mechanical Loading, Mechanotransduction, and Biological Responses in Musculoskeletal Tissues Across the Lifespan: Regulation Influenced by Cells, Extracellular Matrix, and Sex.Results and problems in cell differentiation · 2026Review
- Cell Motility Dynamics in Glaucoma: Mechanisms, Pathogenic Roles, and Therapeutic Targeting.Medicina (Kaunas, Lithuania) · 2025Review
- The TRPV4-YAP axis mediates cytoskeletal and extracellular matrix remodeling in trabecular meshwork cells as a novel glaucoma mechanism.Scientific reports · 2025Article
- Mechano- and Glucocorticoid-Sensitive TREK-1 Channels Regulate Conventional Outflow and Intraocular Pressure.Investigative ophthalmology & visual science · 2025Article
- Transient receptor potential vanilloid 4 modulates substrate stiffness mechanosensing and transcellular pore formation in human Schlemm's canal cells.Acta biomaterialia · 2025Article
- Review
- TRPV4 controls circadian and pathological ocular hypertension.The Journal of physiology · 2025Article
- TRPV4 activation by TGFβ2 enhances cellular contractility and drives ocular hypertension.eLife · 2025Article
- Biomechanical properties of the trabecular meshwork in intraocular pressure regulation: a review.International ophthalmology · 2025Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Intraocular pressure (IOP) is dynamically regulated by the trabecular meshwork (TM), a mechanosensitive tissue that protects the eye from injury through dynamic regulation of aqueous humor flow. TM compensates for mechanical stress impelled by chronic IOP elevations through increased actin polymerization, tissue stiffness, and contractility. This process has been associated with open angle glaucoma; however, the mechanisms that link mechanical stress to pathological cytoskeletal remodeling downstream from the mechanotransducers remain poorly understood. We used fluorescence imaging and biochemical analyses to investigate cytoskeletal and focal adhesion remodeling in human TM cells stimulated with physiological strains. Mechanical stretch promoted F-actin polymerization, increased the number and size of focal adhesions, and stimulated the activation of the Rho-associated protein kinase (ROCK). Stretch-induced activation of the small GTPase Ras homolog family member A (RhoA), and tyrosine phosphorylations of focal adhesion proteins paxillin, focal adhesion kinase (FAK), vinculin, and zyxin were time dependently inhibited by ROCK inhibitor trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohexanecarboxamide dihydrochloride (Y-27632), and by HC-067047, an antagonist of transient receptor potential vanilloid 4 (TRPV4) channels. Both TRPV4 and ROCK activation were required for zyxin translocation and increase in the number/size of focal adhesions in stretched cells. Y-27632 blocked actin polymerization without affecting calcium influx induced by membrane stretch and the TRPV4 agonist GSK1016790A. These results reveal that mechanical tuning of TM cells requires parallel activation of TRPV4, integrins, and ROCK, with chronic stress leading to sustained remodeling of the cytoskeleton and focal complexes.
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