title: Nitric oxide (NO): an emerging target for the treatment of glaucoma.
abstract: The predominant risk factor for the progression of glaucoma is an increase in IOP, mediated via a reduction in aqueous outflow through the conventional (trabecular meshwork and Schlemm's canal) outflow pathway. Current IOP lowering pharmacological strategies target the uveoscleral (nonconventional) outflow pathway or aqueous humor production; however, to date no therapy that primarily targets the conventional pathway exists. Nitric oxide (NO) is an intracellular signaling molecule produced by endogenous NO synthases, well-known for its key role in vasodilation, through its action on smooth muscle cells. Under physiological conditions, NO mediates a multitude of diverse ocular effects, including maintenance of IOP. Nitric oxide donors have been shown to mediate IOP-lowering effects in both preclinical models and clinical studies, primarily through cell volume and contractility changes in the conventional outflow tissues. This review is focused on evaluating the current knowledge of the role and mechanism of action of endogenous NO and NO donors in IOP regulation. Data on key additional functions of NO in glaucoma pathology (i.e., ocular blood flow and effects on optic neuropathy) are also summarized. The potential for future therapeutic application of NO in the treatment of glaucoma is then discussed.
authors.affiliation: Bausch & Lomb, Inc., Rochester, New York, United States.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Cavet
authors.affiliation: Bausch & Lomb, Inc., Bridgewater, New Jersey, United States.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Vittitow
authors.affiliation: Nicox Research Institute, Bresso, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Impagnatiello
authors.affiliation: Nicox Research Institute, Bresso, Milan, Italy.
authors.forename: Ennio
authors.initials: E
authors.lastname: Ongini
authors.affiliation: Nicox Research Institute, Bresso, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bastia
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D045462:Endothelium-Dependent Relaxing Factors / Q000627:therapeutic use; D005901:Glaucoma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D009569:Nitric Oxide / Q000627:therapeutic use*; D018384:Oxidative Stress
chemical_list: D045462:Endothelium-Dependent Relaxing Factors; D009569:Nitric Oxide
keywords: aqueous outflow; intraocular pressure; nitric oxide