Mechanotransduction in trabecular meshwork cells: Rho/ROCK-dependent responses to substrate stiffness

IF 2.9 3区医学 Q3 BIOPHYSICS

Journal of biomechanics Pub Date : 2026-03-01 Epub Date: 2026-01-12 DOI:10.1016/j.jbiomech.2026.113164

Ruotian Du , Jing Ji , Dongyan Li , Long Li , Fan Song , Yubo Fan

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引用次数: 0

Abstract

Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. Trabecular meshwork cells (TMCs) play a crucial role in modulating IOP by regulating the aqueous outflow resistance. In glaucoma, the stiffening of trabecular meshwork (TM) tissue is believed to affect aqueous humor outflow, highlighting the importance of substrate stiffness in influencing TMC behavior. However, the molecular mechanisms by which substrate stiffness impacts TMCs are still not fully understood. This study investigates the role of the Rho/ROCK pathway in the effect of substrate stiffness on TMCs. Human TMCs (hTMCs) and porcine TMCs (pTMCs) were cultured on substrates of varying stiffness with Rho/ROCK pathway inhibitor Y-27632 to assess the alterations in Rho/ROCK pathway molecules, cytoskeletal organization, and cellular functions. The results indicate that stiffer substrates generally lead to decreased ROCK levels, multi-oriented F-actin organization, increased cellular contraction, and enhanced cell migration. Notably, these effects were diminished or negated by Rho/ROCK pathway inhibition, which suggests that the Rho/ROCK pathway is at least partially responsible for mediating substrate stiffness affecting TMC behavior. This study highlights the significance of the mechano-microenvironment of the TM in glaucoma pathogenesis and deepens the understanding of the Rho/ROCK pathway as a promising therapeutic target for glaucoma treatment.

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小梁网细胞的机械转导：Rho/ rock对基质刚度的依赖反应

眼压升高是青光眼的主要危险因素。小梁网细胞（TMCs）通过调节水流出阻力在眼内压调节中起重要作用。在青光眼中，小梁网（TM）组织的硬化被认为影响房水流出，强调了基底刚度在影响小梁网行为中的重要性。然而，衬底刚度影响tmc的分子机制仍未完全了解。本研究探讨了Rho/ROCK通路在基质刚度对tmc的影响中的作用。将人TMCs （hTMCs）和猪TMCs （pTMCs）培养在含有Rho/ROCK途径抑制剂Y-27632的不同硬度底物上，以评估Rho/ROCK途径分子、细胞骨架组织和细胞功能的变化。结果表明，较硬的底物通常会导致ROCK水平降低、多取向f -肌动蛋白组织、细胞收缩增加和细胞迁移增强。值得注意的是，这些影响被Rho/ROCK途径抑制所减弱或否定，这表明Rho/ROCK途径至少部分负责介导影响TMC行为的底物刚度。本研究强调了TM的机械微环境在青光眼发病机制中的重要意义，加深了对Rho/ROCK通路作为青光眼治疗靶点的认识。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of biomechanics 生物-工程：生物医学

CiteScore

5.10

自引率

4.20%

发文量

345

审稿时长

1 months

期刊介绍： The Journal of Biomechanics publishes reports of original and substantial findings using the principles of mechanics to explore biological problems. Analytical, as well as experimental papers may be submitted, and the journal accepts original articles, surveys and perspective articles (usually by Editorial invitation only), book reviews and letters to the Editor. The criteria for acceptance of manuscripts include excellence, novelty, significance, clarity, conciseness and interest to the readership. Papers published in the journal may cover a wide range of topics in biomechanics, including, but not limited to: -Fundamental Topics - Biomechanics of the musculoskeletal, cardiovascular, and respiratory systems, mechanics of hard and soft tissues, biofluid mechanics, mechanics of prostheses and implant-tissue interfaces, mechanics of cells. -Cardiovascular and Respiratory Biomechanics - Mechanics of blood-flow, air-flow, mechanics of the soft tissues, flow-tissue or flow-prosthesis interactions. -Cell Biomechanics - Biomechanic analyses of cells, membranes and sub-cellular structures; the relationship of the mechanical environment to cell and tissue response. -Dental Biomechanics - Design and analysis of dental tissues and prostheses, mechanics of chewing. -Functional Tissue Engineering - The role of biomechanical factors in engineered tissue replacements and regenerative medicine. -Injury Biomechanics - Mechanics of impact and trauma, dynamics of man-machine interaction. -Molecular Biomechanics - Mechanical analyses of biomolecules. -Orthopedic Biomechanics - Mechanics of fracture and fracture fixation, mechanics of implants and implant fixation, mechanics of bones and joints, wear of natural and artificial joints. -Rehabilitation Biomechanics - Analyses of gait, mechanics of prosthetics and orthotics. -Sports Biomechanics - Mechanical analyses of sports performance.