FP and EP2 prostanoid receptor agonist drugs and aqueous humor outflow devices for treating ocular hypertension and glaucoma

Najam A Sharif; Noriko Odani-Kawabata; Fenghe Lu; Leonard Pinchuk

doi:10.1016/j.exer.2023.109415

FP and EP2 prostanoid receptor agonist drugs and aqueous humor outflow devices for treating ocular hypertension and glaucoma

Exp Eye Res. 2023 Apr:229:109415. doi: 10.1016/j.exer.2023.109415. Epub 2023 Feb 18.

Authors

Najam A Sharif¹, Noriko Odani-Kawabata², Fenghe Lu³, Leonard Pinchuk⁴

Affiliations

¹ Ophthalmology Innovation Center, Santen Inc., Emeryville, CA, USA; Singapore Eye Research Institute, Singapore; Eye-ACP Duke-National University of Singapore Medical School, Singapore; Department of Pharmacology and Neuroscience, University of North Texas Health Sciences Center, Fort Worth, TX, USA; Department of Pharmacy Sciences, Creighton University, Omaha, NE, USA; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA; Imperial College of Science and Technology, St. Mary's Campus, London, UK; Institute of Ophthalmology, University College London, London, UK. Electronic address: najam.sharif@santen.com.
² Product Development Division, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
³ Product Development Division, Santen Inc., Emeryville, CA, USA.
⁴ Ophthalmology Innovation Center, Santen Inc., Emeryville, CA, USA; Biomedical Engineering Department, University of Miami, Miami, FL, USA.

PMID: 36803996
DOI: 10.1016/j.exer.2023.109415

Abstract

Prostaglandin (PG) receptors represent important druggable targets due to the many diverse actions of PGs in the body. From an ocular perspective, the discovery, development, and health agency approvals of prostaglandin F (FP) receptor agonists (FPAs) have revolutionized the medical treatment of ocular hypertension (OHT) and glaucoma. FPAs, such as latanoprost, travoprost, bimatoprost, and tafluprost, powerfully lower and control intraocular pressure (IOP), and became first-line therapeutics to treat this leading cause of blindness in the late 1990s to early 2000s. More recently, a latanoprost-nitric oxide (NO) donor conjugate, latanoprostene bunod, and a novel FP/EP3 receptor dual agonist, sepetaprost (ONO-9054 or DE-126), have also demonstrated robust IOP-reducing activity. Moreover, a selective non-PG prostanoid EP2 receptor agonist, omidenepag isopropyl (OMDI), was discovered, characterized, and has been approved in the United States, Japan and several other Asian countries for treating OHT/glaucoma. FPAs primarily enhance uveoscleral (UVSC) outflow of aqueous humor (AQH) to reduce IOP, but cause darkening of the iris and periorbital skin, uneven thickening and elongation of eyelashes, and deepening of the upper eyelid sulcus during chronic treatment. In contrast, OMDI lowers and controls IOP by activation of both the UVSC and trabecular meshwork outflow pathways, and it has a lower propensity to induce the aforementioned FPA-induced ocular side effects. Another means to address OHT is to physically promote the drainage of the AQH from the anterior chamber of the eye of patients with OHT/glaucoma. This has successfully been achieved by the recent approval and introduction of miniature devices into the anterior chamber by minimally invasive glaucoma surgeries. This review covers the three major aspects mentioned above to highlight the etiology of OHT/glaucoma, and the pharmacotherapeutics and devices that can be used to combat this blinding ocular disease.

Keywords: EP2 receptor agonist; FP receptor agonist; Glaucoma; MIGS; Ocular hypertension; Omidenepag; Omidenepag isopropyl; Prostaglandin.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antihypertensive Agents / therapeutic use
Aqueous Humor / metabolism
Glaucoma* / drug therapy
Glaucoma* / metabolism
Humans
Intraocular Pressure
Latanoprost
Ocular Hypertension* / drug therapy
Ocular Hypertension* / metabolism

Substances

Latanoprost
Antihypertensive Agents