Investigational Rho Kinase Inhibitors for the Treatment of Glaucoma

Abstract

Ghadeer Al-Humimat1 12 2, Ibtisam Marashdeh2 2, Duaa Daradkeh2 2, Karanjit Kooner1 13 3 1Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USA; 2Department of Ophthalmology, King Hussein Medical Center, Amman, Jordan; 3Department of Ophthalmology, Veteran Affairs North Texas Health Care System Medical Center Dallas, Dallas, TX, USACorrespondence: Karanjit KoonerDepartment of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390, USATel [phone]Fax [phone]Email [email protected]: This review provides a comprehensive update on emerging ROCK inhibitors as an innovative treatment option for lowering intraocular pressure (IOP) in glaucoma and aims to describe the structure, mechanism of action, pharmaceutical characteristics, desirable ocular effects, including side effects for each agent. A literature review was conducted using PubMed, Scopus, clinicaltrials.gov, ARVO journals, Cochrane library and Selleckchem. Databases were searched using “investigational Rho kinase inhibitors,” and “glaucoma” as keywords. In addition to this building block strategy, successive fractions were employed to further refine the results. Of the several ROCK inhibitors discovered, only two drugs are currently approved for glaucoma treatment; Netarsudil in the USA and Ripasudil in Japan and China. We identified and reviewed 15 agents currently in laboratory or clinical trials. These agents lower IOP mainly by decreasing outflow resistance through pharmacologic relaxation of the trabecular meshwork (TM) cells and reducing episcleral venous pressure. They have an optimistic safety profile; however, conjunctival hyperemia, conjunctival hemorrhage, pain on instillation, and corneal verticillata are common. Other properties such as neuroprotection (enhancing optic nerve blood flow and promoting axonal regeneration), anti-fibrotic activity, and endothelial cell proliferation may improve the visual prognosis and surgical outcomes in glaucoma. In addition, these agents have the potential to work synergistically with other topical glaucoma medications.Keywords: rho kinase inhibitors, ROCK, glaucoma, intraocular pressure, trabecular meshwork, Schlemm’s canal

Keywords

• rho kinase inhibitors
• rock
• glaucoma
• intraocular pressure
• trabecular meshwork
• schlemm’s canal.