The Rho GTPase and Rho kinase (ROCK) signaling pathway is essential for cellular mechanics, acting as key regulators of the actin cytoskeleton and actomyosin contractility in various cell types and tissues. Rho GTPases, functioning as molecular switches, and ROCKs, their primary downstream effectors, influence vital cellular processes such as cell shape, movement, growth, and gene regulation. This review explores how this pathway maintains tissue tone, especially its significant role in regulating trabecular meshwork (TM) contractility. It also highlights the critical part of the Rho-ROCK pathway in precisely managing intraocular pressure (IOP). Dysregulation of Rho/ROCK signaling is a known factor in increased aqueous humor (AH) outflow resistance, a major cause of glaucoma, which is a leading cause of irreversible blindness worldwide. The review discusses the molecular mechanisms behind these processes, illustrating how the pathway affects the contractile behavior of tissues in the AH outflow pathway—including the TM and Schlemm’s canal (SC)—by directly impacting actomyosin dynamics and extracellular matrix (ECM) remodeling. It also examines the extensive interaction between Rho/ROCK and other vital signaling pathways such as MAPK/ERK and serum response factor (SRF), emphasizing its integrated role within the complex cellular signaling systems in the AH drainage pathway. This comprehensive discussion concludes by highlighting the promising therapeutic potential of Rho kinase inhibitors (RKIs) as a new class of drugs for glaucoma. These agents not only effectively lower IOP but also show emerging neuroprotective properties, with broader implications for other eye and systemic diseases. Understanding this pathway—from its molecular structure to clinical applications—provides a strong foundation for future research and the development of more precise interventions.
Raghavan et al. (2026) studied this question.