Transforming Growth Factor beta-2 (TGFβ2) Drives Trabecular Meshwork Progenitor Cell Differentiation Through SMAD2/3 Signalling.

Fan, Xiaochen ORCID: 0000-0002-7116-2846, Bilir, Emine K ORCID: 0000-0003-4499-6543, Kingston, Olivia A, Kearns, Victoria R, Willoughby, Colin E ORCID: 0000-0002-1246-4166 and Sheridan, Carl M ORCID: 0000-0003-0100-9587 (2026) Transforming Growth Factor beta-2 (TGFβ2) Drives Trabecular Meshwork Progenitor Cell Differentiation Through SMAD2/3 Signalling. Stem cells (Dayton, Ohio). sxag033-. ISSN 1066-5099, 1549-4918

Access the full-text of this item by clicking on the Open Access link.

Abstract

Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness, yet its underly mechanisms remain unclear. Elevated intraocular pressure (IOP), the only modifiable risk factor for POAG, arises from increased resistance to aqueous humour outflow within the conventional outflow pathway, which comprises the trabecular meshwork (TM) and the inner wall of Schlemm's canal. Dysfunction and cellular loss within this pathway, particularly in the TM, are consistent features of the disease; however, the mechanisms responsible for impaired tissue maintenance and regenerative failure remain unclear. Trabecular meshwork progenitor cells (TMPCs) have the capacity to replace lost TM cells, suggesting that impaired progenitor function may contribute to disease progression. Transforming growth factor beta 2 (TGFβ2), which is consistently elevated in the aqueous humour of POAG patients, plays a key role in regulating stem cell differentiation. We proposed that excess TGFβ2 disrupts TMPC function, leading to progenitor depletion and TM dysfunction. Here, we show that TGFβ2 drives TMPCs toward a differentiated, fibrotic phenotype, increasing TM and profibrotic gene expression while reducing progenitor markers. These effects are mediated through TGFβ2-SMAD2/3 signalling, as inhibition of this pathway preserves TMPC characteristics and suppresses fibrotic gene induction. Our findings identify TGFβ2-SMAD2/3 signalling as a regulator of TMPC fate in vitro and suggest a potential mechanism by which elevated TGFβ2 may influence TM progenitor cell behaviour under pathological conditions.

Item Type:	Article
Uncontrolled Keywords:	TGFβ, cell differentiation, glaucoma, progenitor cells, trabecular meshwork
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Inst. Life Courses & Medical Sciences (T&R staff) Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Eye & Vision Sciences
Depositing User:	Symplectic Admin
Date Deposited:	02 Jul 2026 14:49
Last Modified:	02 Jul 2026 14:49
DOI:	10.1093/stmcls/sxag033
Open Access URL:	https://academic.oup.com/stmcls/advance-article/do...
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3199249
Disclaimer:	The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate.