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

• Published in: Experimental eye research Vol. 229; p. 109415
• Main Authors: Sharif, Najam A., Odani-Kawabata, Noriko, Lu, Fenghe, Pinchuk, Leonard
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2023
• Subjects: Antihypertensive Agents - therapeutic use; Aqueous Humor - metabolism; EP2 receptor agonist; FP receptor agonist; Glaucoma; Glaucoma - drug therapy; Glaucoma - metabolism; Humans; Intraocular Pressure; Latanoprost; MIGS; Ocular hypertension; Ocular Hypertension - drug therapy; Ocular Hypertension - metabolism; Omidenepag; Omidenepag isopropyl; Prostaglandin; Glaucoma; FP receptor agonist; Omidenepag isopropyl; Prostaglandin; Ocular hypertension; EP2 receptor agonist; MIGS; Omidenepag
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2023.109415

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. [Display omitted] •Prostaglandin (PG) FP receptor agonist analogs (e.g., latanoprost; travoprost) and their conjugates are first-line therapeutics that lower elevated intraocular pressure (IOP).•Recently a novel non-PG EP2 receptor agonist, omidenepag isopropyl (OMDI; Eybelis; Omlonti), was approved to treat ocular hypertension and glaucoma.•Omidenepag, acid form of OMDI, increases cAMP, relaxes trabecular meshwork (TM) and ciliary muscle and enhances aqueous humor (AQH) outflow via TM and uveoscleral pathways to lower IOP.•Miniature devices inserted into the anterior chamber of the eye also powerfully lower IOP by draining AQH.