Mechanism of Action
The Rho family of G proteins are activated by various cytokines and regulate various aspects of cell structure, including cell stiffness, cell morphology, cell adhesion, apoptosis, and smooth muscle contraction. The effectors of these G proteins are the Rho kinases (ROCK1 and ROCK2). Activated Rho kinase phosphorylates various downstream proteins, including myosin light chain (MLC) phosphatase.
The net result of Rho kinase activity is increased phosphorylation and activation of MLC. Phosphorylated MLC interacts with actin, altering the physical characteristics of the cytoskeleton and thereby leading to increased cell stiffness and smooth muscle cell contraction. Rho kinase inhibitors lower IOP primarily by relaxing the cytoskeleton of outflow cells in the trabecular meshwork and Schlemm canal, increasing conventional (trabecular) outflow facility.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.