Prostaglandin analogues and nitric oxide contribution in the treatment of ocular hypertension and glaucoma

Abstract

In patients with ocular hypertension or glaucoma, all treatments aim to lower intraocular pressure (IOP) by modulating aqueous humour (AH) production and/or uveoscleral and trabecular meshwork/Schlemm's canal AH drainage. PG analogues are considered to be the 'gold standard' treatment and are the most frequently used IOP-lowering agents. Recent data support an important role for NO in regulating IOP. Thus, novel PG analogues carrying a NO-donating moiety were recently advanced. Latanoprostene bunod (LBN) and NCX 470, NO-donating derivatives of latanoprost and bimatoprost, respectively, are examples of such compounds. LBN ophthalmic solution, 0.024% (Vyzulta™), showed greater IOP-lowering efficacy compared with that of Xalatan (latanoprost ophthalmic solution, 0.005%) or 0.5% timolol maleate in clinical settings. NCX 470 was found to be more effective than bimatoprost in animal models of ocular hypertension and glaucoma. Selective EP receptor agonists (i.e. taprenepag isopropyl, omidenepag isopropyl and aganepag isopropyl) and non-selective prostanoid receptor agonists (i.e. ONO-9054, sepetaprost isopropyl) that concomitantly stimulate FP and EP receptors have also been shown to hold promise as effective IOP-lowering agents.

Comparative evaluation of Latanoprostene Bunod, Timolol Maleate, and latanoprost Ophthalmic Solutions to assess their safety and efficacy in lowering intraocular pressure for the management of Open-Angle Glaucoma

“…Latanoprostene bunod is hydrolyzed by corneal esterases to the prostanoid FP receptor agonist latanoprost acid (active metabolite) and butanediol mononitrate, which is further metabolized to 1.4-butanediol and nitric oxide (NO) (active metabolite) ( 8 ). Latanoprost acid increases matrix metalloproteinase (MMP)-1, MMP-3, and MMP-9 expression in the ciliary muscles, promoting the remodeling of the extracellular matrix and, subsequently, increases aqueous humor outflow through the uveoscleral pathway ( 8 , 9 ). The efficacy of timolol ophthalmic solution in the reduction of IOP has also been reported ( 10 , 11 ).…”

Omidenepag, a non-prostanoid EP2 receptor agonist, induces enlargement of the 3D organoid of 3T3-L1 cells

“…It is well known that prostaglandins (PGs) are involved in various physiological and pathological functions such as regulation of smooth muscles, inflammation, immune response, and others 1 . Camras et al first reported that the topical administration of PGF2α and PGE2 decreases intraocular pressure (IOP) in rabbits, and suggested that the stimulation of the prostanoid FP receptors and PGE2 receptors (mainly EP2 and EP3) represent a potentially novel therapy for the treatment of patients with ocular hypertensive (OH) and glaucoma 2 .…”

Profiling ocular surface responses to preserved and non‐preserved topical glaucoma medications: A 2‐year randomized evaluation study

“…Clinical studies have shown that patients on bimatoprost frequently develop ocular hyperemia 43‐46 . This effect of bimatoprost 0.03% on OS has been confirmed to be due to vasodilation mediated via over‐production of nitric oxide synthase, but not due to the induction of inflammatory cytokines 43,47 …”