ArticleInvestigative ophthalmology & visual science2016
The Soluble Guanylate Cyclase Stimulator IWP-953 Increases Conventional Outflow Facility in Mouse Eyes.
Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- Cell senescence alters responses of porcine trabecular meshwork cells to shear stress.Frontiers in cell and developmental biology · 2022Article
- The Application of Nitric Oxide for Ocular Hypertension Treatment.Molecules (Basel, Switzerland) · 2021Review
- The vital role for nitric oxide in intraocular pressure homeostasis.Progress in retinal and eye research · 2021Review
- Nitric oxide attenuated transforming growth factor-β induced myofibroblast differentiation of human keratocytes.Scientific reports · 2021Article
- Soluble Guanylate Cyclase Stimulators and Activators.Handbook of experimental pharmacology · 2021Article
- The nitric oxide-guanylate cyclase pathway and glaucoma.Nitric oxide : biology and chemistry · 2018Review
- Structure/function of the soluble guanylyl cyclase catalytic domain.Nitric oxide : biology and chemistry · 2018Review
- Consensus recommendations for trabecular meshwork cell isolation, characterization and culture.Experimental eye research · 2018Review
- The Ability of Nitric Oxide to Lower Intraocular Pressure Is Dependent on Guanylyl Cyclase.Investigative ophthalmology & visual science · 2017Article
- The many faces of the trabecular meshwork cell.Experimental eye research · 2017Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe nitric oxide (NO)-cyclic guanosine-3',5'-monophosphate (cGMP) pathway regulates aqueous humor outflow and therefore, intraocular pressure. We investigated the pharmacologic effects of the soluble guanylate cyclase (sGC) stimulator IWP-953 on primary human trabecular meshwork (HTM) cells and conventional outflow facility in mouse eyes.
methodsCyclic GMP levels were determined in vitro in HEK-293 cells and four HTM cell strains (HTM120/HTM123: predominantly myofibroblast-like phenotype, HTM130/HTM141: predominantly endothelial-like phenotype), and in HTM cell culture supernatants. Conventional outflow facility was measured following intracameral injection of IWP-953 or DETA-NO using a computerized pressure-controlled perfusion system in enucleated mouse eyes ex vivo.
resultsIWP-953 markedly stimulated cGMP production in HEK-293 cells in the presence and absence of DETA-NO (half maximal effective concentrations: 17 nM, 9.5 μM). Similarly, IWP-953 stimulated cGMP production in myofibroblast-like HTM120 and HTM123 cells, an effect that was greatly amplified by the presence of DETA-NO. In contrast, IWP-953 stimulation of cGMP production in endothelial-like HTM130 and HTM141 cells was observed, but was markedly less prominent than in HTM120 and HTM123 cells. Notably, cGMP was found in all HTM culture supernatants, following IWP-953/DETA-NO stimulation. In paired enucleated mouse eyes, IWP-953 at 10, 30, 60, and 100 μM concentration-dependently increased outflow facility. This effect (89.5%) was maximal at 100 μM (P = 0.002) and in magnitude comparable to DETA-NO at 100 μM (97.5% increase, P = 0.030).
conclusionsThese data indicate that IWP-953, via modulation of the sGC-cGMP pathway, increases aqueous outflow facility in mouse eyes, suggesting therapeutic potential for sGC stimulators as novel ocular hypotensive drugs.
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