Integrin α4 and α9 in trabecular meshwork and Schlemm's canal function: emerging regulators of intraocular pressure homeostasis.

Integrins are hetero-dimeric transmembrane receptors that facilitate bidirectional signaling between the extracellular matrix and the intracellular environment. Among these, the α4 and α9 subunits form a distinct subfamily when paired with the β1 integrin subunit. α4β1 and α9β1 integrins play specialized roles in cell migration, adhesion, and mechanotransduction. In the ocular anterior segment, these integrins are recognized for their contributions to the physiological function of the trabecular meshwork (TM) and Schlemm's canal (SC). This review examines the structural and functional characteristics of α4β1 and α9β1, their involvement in aqueous humor (AH) outflow and intraocular pressure (IOP) regulation, and their specific interactions with the fibronectin extra domain A (FN+EDA). Furthermore, we explore the crosstalk between these integrins and the toll-like receptor 4 (TLR4) and transforming growth factor-beta (TGFβ) signaling pathways, highlighting their potential role in driving a fibrotic-like response observed in the glaucomatous TM.