TGF-β2/OPTN/FOXC1/miR-200 axis regulates actin dynamics in human trabecular meshwork cells.

Glaucoma is the second leading cause of irreversible blindness globally, with elevated intraocular pressure (IOP) being its primary risk factor. Current therapeutic approaches, such as beta-blockers, alpha-adrenergic agonists, Rho-kinase inhibitors, etc., aim to reduce IOP levels. However, the molecular mechanisms underlying altered IOP remain poorly understood. In this study, we have treated primary human trabecular meshwork cells (HTM) with exogenous dexamethasone (dex) or transforming growth factor beta-2 (TGF-β2) to investigate their effects on glaucoma candidate genes. Interestingly, our findings reveal that FOXC1 acts as a repressor of CYP1B1, and optineurin (OPTN) facilitates the ubiquitination of FOXC1, thereby inducing the expression of CYP1B1. Furthermore, we found that the miR-200 family and other miRNAs regulate these glaucoma candidate genes. Furthermore, TGF-β2 downregulates the miR-200 family, whereas the miR-200 family targets FOXC1, exerting reversible effects by altering the extracellular matrix. Thus, modulating the TGF-β2/OPTN/FOXC1/miR-200 axis appears critical in regulating actin dynamics in the anterior eye segment.