Pro-fibrotic signaling in trabecular meshwork cells

Pro-fibrotic signaling in trabecular meshwork (TM) cells refers to the complex network of intracellular and extracellular pathways that drive the pathological accumulation of extracellular matrix (ECM) and increased cellular contractility within the eye's drainage tissues. This process is primarily mediated by Transforming Growth Factor-beta 2 (TGF-beta2), which triggers downstream cascades including the Smad pathway and non-Smad pathways like Rho/ROCK and YAP/TAZ signaling. In a healthy state, the TM regulates the outflow of aqueous humor to maintain stable intraocular pressure; however, chronic activation of pro-fibrotic signaling leads to TM stiffening and increased outflow resistance. This mechanical and biochemical transformation is a hallmark of primary open-angle glaucoma. Therapeutic strategies targeting this process include ROCK inhibitors, which reduce cell contractility, and experimental TGF-beta antagonists or SMAD inhibitors aimed at halting the fibrotic progression.

Other names

TGF-beta signaling in trabecular meshworkTM fibrosis pathwayTrabecular meshwork ECM remodelingTGF-beta2-induced fibrosis

Inhibition of Rho-associated protein kinase (ROCK) to reduce actin-myosin contractility and ECM production; antagonism of TGF-beta receptors to block Smad-mediated transcriptional activation of pro-fibrotic genes; modulation of adenosine receptors to enhance aqueous outflow.