Rho/Rho-associated kinase pathway in glaucoma (Review)

The Rho/ROCK pathway plays important roles in the modulation of the cytoskeletal integrity of cells, the synthesis of extracellular matrix components in the aqueous humor outflow tissue and the permeability of Schlemm's canal endothelial cells. The activation of the Rho/ROCK pathway results in trabecular meshwork (TM) contraction, and the inhibition of this pathway would provoke relaxation of TM with subsequent increase in outflow facility and, thereby, decrease intraocular pressure (IOP). ROCK inhibitors also serve as potent antiscarring agents via inhibition of transdifferentiation of tenon fibroblasts into myofibroblasts. Furthermore, the RhoA/ROCK pathway is involved in optic nerve neuroprotection. Inactivation of Rho/ROCK signaling increase ocular blood flow, improve retinal ganglion cell (RGC) survival and promote RGC axon regeneration. Considering the IOP modulation, potent bleb anti-scarring effect and neuroprotective properties of ROCK inhibitors, the Rho/ROCK pathway is an attractive target for anti-glaucoma therapy, and it may be used for human therapy in the near future.