Rho-Associated Protein Kinase Inhibitors and Primary Open-Angle Glaucoma
Rho-associated protein kinase (ROCK) inhibitors have been broadly investigated over the past 15 years as potential agents for the treatment of elevated intraocular pressure (IOP) secondary to primary open-angle glaucoma (POAG). 1, 2 Preclinical and clinical evidence has suggested that ROCK inhibitors can lower IOP through a unique mechanism of action heretofore untargeted by current ocular hypotensive drugs. 3-9 Mechanistically, ROCK inhibitors can lower IOP through their ability to induce changes in the tissue of the conventional outflow pathway of the anterior chamber, which includes: (1) disassembly of cell-cell junctions and subsequent loosening of the paracellular spaces between cells and (2) general relaxation of contractile tone. Both physiologic actions can improve outflow facility of aqueous humor from the anterior chamber. 3, 4, 10 Furthermore, ROCK inhibitors have been postulated to enhance blood flow to the optic nerve, which serves to ameliorate nerve destruction and potentially preserve sight. 11 The purpose of this chapter is to analyze the evolving role of ROCK inhibitors in the treatment of POAG. While the authors recognize that ROCK inhibitors have been studied for the treatment of other forms of glaucoma, the primary focus of this chapter will be their use in POAG.
