Effects of selective EP2 receptor agonist, omidenepag, on trabecular meshwork cells, Schlemm’s canal endothelial cells and ciliary muscle contraction

Abstract This study investigated the effects of omidenepag (OMD), a novel selective EP2 receptor agonist, on human trabecular meshwork (HTM) cells, monkey Schlemm’s canal endothelial (SCE) cells, and porcine ciliary muscle (CM) to clarify the mechanism of intraocular pressure (IOP) reduction involvi...

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Autores principales:	Natsuko Nakamura, Megumi Honjo, Reiko Yamagishi, Nozomi Igarashi, Rei Sakata, Makoto Aihara
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dccdf48355c74765b1d9b965b6374adf
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spelling	oai:doaj.org-article:dccdf48355c74765b1d9b965b6374adf2021-12-02T18:50:47ZEffects of selective EP2 receptor agonist, omidenepag, on trabecular meshwork cells, Schlemm’s canal endothelial cells and ciliary muscle contraction10.1038/s41598-021-95768-z2045-2322https://doaj.org/article/dccdf48355c74765b1d9b965b6374adf2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95768-zhttps://doaj.org/toc/2045-2322Abstract This study investigated the effects of omidenepag (OMD), a novel selective EP2 receptor agonist, on human trabecular meshwork (HTM) cells, monkey Schlemm’s canal endothelial (SCE) cells, and porcine ciliary muscle (CM) to clarify the mechanism of intraocular pressure (IOP) reduction involving conventional outflow pathway. In HTM and SCE cells, the effects of OMD on transforming growth factor-β2 (TGF-β2)-induced changes were examined. The expression of actin cytoskeleton and extracellular matrix (ECM) proteins, myosin light chain (MLC) phosphorylation in HTM cells were evaluated using real-time quantitative PCR, immunocytochemistry, and western blotting. The expression of barrier-related proteins, ZO-1 and β-catenin, and permeability of SCE cells were evaluated using immunocytochemistry and transendothelial electrical resistance. The CM contraction was determined by contractibility assay. OMD significantly inhibited expression of TGF-β2 induced mRNA, protein, and MLC-phosphorylation on cytoskeletal and ECM remodeling in the HTM dose dependently. In SCE cells, OMD suppressed TGF-β2-induced expression of the barrier-related proteins and decreased SCE monolayer permeability. OMD at 3 µM significantly inhibited CM contraction, however, the effect was not significant at lower concentrations. IOP lowering effect of OMD through conventional outflow pathway is exerted by increasing outflow facilities with the modulation of TM cell fibrosis and SCE cell permeability.Natsuko NakamuraMegumi HonjoReiko YamagishiNozomi IgarashiRei SakataMakoto AiharaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Natsuko Nakamura Megumi Honjo Reiko Yamagishi Nozomi Igarashi Rei Sakata Makoto Aihara Effects of selective EP2 receptor agonist, omidenepag, on trabecular meshwork cells, Schlemm’s canal endothelial cells and ciliary muscle contraction
description	Abstract This study investigated the effects of omidenepag (OMD), a novel selective EP2 receptor agonist, on human trabecular meshwork (HTM) cells, monkey Schlemm’s canal endothelial (SCE) cells, and porcine ciliary muscle (CM) to clarify the mechanism of intraocular pressure (IOP) reduction involving conventional outflow pathway. In HTM and SCE cells, the effects of OMD on transforming growth factor-β2 (TGF-β2)-induced changes were examined. The expression of actin cytoskeleton and extracellular matrix (ECM) proteins, myosin light chain (MLC) phosphorylation in HTM cells were evaluated using real-time quantitative PCR, immunocytochemistry, and western blotting. The expression of barrier-related proteins, ZO-1 and β-catenin, and permeability of SCE cells were evaluated using immunocytochemistry and transendothelial electrical resistance. The CM contraction was determined by contractibility assay. OMD significantly inhibited expression of TGF-β2 induced mRNA, protein, and MLC-phosphorylation on cytoskeletal and ECM remodeling in the HTM dose dependently. In SCE cells, OMD suppressed TGF-β2-induced expression of the barrier-related proteins and decreased SCE monolayer permeability. OMD at 3 µM significantly inhibited CM contraction, however, the effect was not significant at lower concentrations. IOP lowering effect of OMD through conventional outflow pathway is exerted by increasing outflow facilities with the modulation of TM cell fibrosis and SCE cell permeability.
format	article
author	Natsuko Nakamura Megumi Honjo Reiko Yamagishi Nozomi Igarashi Rei Sakata Makoto Aihara
author_facet	Natsuko Nakamura Megumi Honjo Reiko Yamagishi Nozomi Igarashi Rei Sakata Makoto Aihara
author_sort	Natsuko Nakamura
title	Effects of selective EP2 receptor agonist, omidenepag, on trabecular meshwork cells, Schlemm’s canal endothelial cells and ciliary muscle contraction
title_short	Effects of selective EP2 receptor agonist, omidenepag, on trabecular meshwork cells, Schlemm’s canal endothelial cells and ciliary muscle contraction
title_full	Effects of selective EP2 receptor agonist, omidenepag, on trabecular meshwork cells, Schlemm’s canal endothelial cells and ciliary muscle contraction
title_fullStr	Effects of selective EP2 receptor agonist, omidenepag, on trabecular meshwork cells, Schlemm’s canal endothelial cells and ciliary muscle contraction
title_full_unstemmed	Effects of selective EP2 receptor agonist, omidenepag, on trabecular meshwork cells, Schlemm’s canal endothelial cells and ciliary muscle contraction
title_sort	effects of selective ep2 receptor agonist, omidenepag, on trabecular meshwork cells, schlemm’s canal endothelial cells and ciliary muscle contraction
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/dccdf48355c74765b1d9b965b6374adf
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_version_	1718377535811616768

Effects of selective EP2 receptor agonist, omidenepag, on trabecular meshwork cells, Schlemm’s canal endothelial cells and ciliary muscle contraction

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