Topical CAY-10746, a Novel ROCK Inhibitor, Reduces Intraocular Pressure and Modulates the Trabecular Meshwork in Normotensive Rats

BACKGROUND: Elevated intraocular pressure (IOP) is the primary modifiable risk factor for glaucoma. Rho-associated kinase (ROCK) inhibitors lower IOP by targeting the trabecular meshwork (TM) to increase conventional aqueous humor outflow. This study evaluates the IOP-lowering efficacy of CAY-10746, a novel ROCK inhibitor, and investigates its effects on TM structure and gene expression in normotensive rats. METHODS: on human TM cells. RESULTS: < 0.05). RNA-Seq identified 762 differentially expressed genes (DEGs) in the TM. Pathway analysis showed significant enrichment of DEGs related to the extracellular matrix, focal adhesion, and the PI3K-Akt signaling pathway. Key glaucoma-related genes, including FN1, RHO, and CYP1B1, were among those modulated. CONCLUSION: The novel ROCK inhibitor CAY-10746 effectively lowers IOP in normotensive rats. This effect is associated with structural changes (increased porosity) and modulation of gene expression pathways critical to TM function. These findings suggest CAY-10746 is a promising therapeutic candidate for glaucoma that warrants further investigation.