TY - JOUR
T1 - Investigational rho kinase inhibitors for the treatment of glaucoma
AU - Al-Humimat, Ghadeer
AU - Marashdeh, Ibtisam
AU - Daradkeh, Duaa
AU - Kooner, Karanjit
N1 - Funding Information:
Supported in part by an unrestricted grant from the Research to Prevent Blindness, New Y ork, NY : V isual Sciences Core Grant EY020799. Figures 1–4 were created with BioRender (T oronto, ON, Canada). Chemical structures in T able 1 were created with ChemDraw (PerkinElmer , W altham, Massachusettes, USA). Special Thanks to: Ashika Angirekula, Jacob A wkal, Hafsa Zuberi (University of T exas Southwestern Medical Center) and Emily Buchanan (University of T exas at Dallas) for their invaluable assistance in reviewing the background research including designing figures and tables.
Publisher Copyright:
© 2021 Al-Humimat et al.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Glaucoma
KW - Intraocular pressure
KW - ROCK
KW - Rho kinase inhibitors
KW - Schlemm’s canal
KW - Trabecular meshwork
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U2 - 10.2147/JEP.S259297
DO - 10.2147/JEP.S259297
M3 - Review article
C2 - 33664600
AN - SCOPUS:85102289300
SN - 1179-1454
VL - 13
SP - 197
EP - 212
JO - Journal of Experimental Pharmacology
JF - Journal of Experimental Pharmacology
ER -