TRPV4 is activated by mechanical stimulation to induce prostaglandins release in trabecular meshwork, lowering intraocular pressure.

Trabecular meshwork constitutes the conventional outflow pathway and controls intraocular pressure by regulating aqueous outflow. Mechanical stimulation has been studied as one of the triggers to regulate aqueous outflow in trabecular meshwork, but it is not well understood. We investigated that how...

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Autores principales: Takatoshi Uchida, Shota Shimizu, Reiko Yamagishi, Suzumi M Tokuoka, Yoshihiro Kita, Rei Sakata, Megumi Honjo, Makoto Aihara
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Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/8f21891e3fc246dcaaef2b5d7a54f8db
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spelling oai:doaj.org-article:8f21891e3fc246dcaaef2b5d7a54f8db2021-12-02T20:16:38ZTRPV4 is activated by mechanical stimulation to induce prostaglandins release in trabecular meshwork, lowering intraocular pressure.1932-620310.1371/journal.pone.0258911https://doaj.org/article/8f21891e3fc246dcaaef2b5d7a54f8db2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258911https://doaj.org/toc/1932-6203Trabecular meshwork constitutes the conventional outflow pathway and controls intraocular pressure by regulating aqueous outflow. Mechanical stimulation has been studied as one of the triggers to regulate aqueous outflow in trabecular meshwork, but it is not well understood. We investigated that how transient receptor potential cation channel subfamily V member 4 (TRPV4) functions in human trabecular meshwork cells (HTMC) and affects intraocular pressure (IOP). HTMC were treated with TRPV4 siRNA, followed by incubation for 24 hours. We confirmed the suppression of TRPV4 mRNA expression and the reduction of Ca2+ influx by the TRPV4 agonist GSK1016790A in TRPV4 siRNA-treated HTMC. TRPV4 siRNA-treated HTMC exhibited a significant reduction in Ca2+ influx and production of arachidonic acid and prostaglandin (PG) E2 induced by mechanical stretch, and direct activation of TRPV4 by GSK1016790A increased production of arachidonic acid, PGE2, and PGD2 and inhibited gel contraction. Furthermore, TRPV4-deficient mice had higher IOP than wild-type mice, and GSK1016790A administration lowered IOP. These results suggest that TRPV4 mediates the cellular response induced by trabecular meshwork stretch, leading to IOP reduction through the production of prostaglandins and inhibition of cell contraction. Targeting TRPV4 may have therapeutic benefits that lead to lowering IOP in glaucoma patients.Takatoshi UchidaShota ShimizuReiko YamagishiSuzumi M TokuokaYoshihiro KitaRei SakataMegumi HonjoMakoto AiharaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258911 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Takatoshi Uchida
Shota Shimizu
Reiko Yamagishi
Suzumi M Tokuoka
Yoshihiro Kita
Rei Sakata
Megumi Honjo
Makoto Aihara
TRPV4 is activated by mechanical stimulation to induce prostaglandins release in trabecular meshwork, lowering intraocular pressure.
description Trabecular meshwork constitutes the conventional outflow pathway and controls intraocular pressure by regulating aqueous outflow. Mechanical stimulation has been studied as one of the triggers to regulate aqueous outflow in trabecular meshwork, but it is not well understood. We investigated that how transient receptor potential cation channel subfamily V member 4 (TRPV4) functions in human trabecular meshwork cells (HTMC) and affects intraocular pressure (IOP). HTMC were treated with TRPV4 siRNA, followed by incubation for 24 hours. We confirmed the suppression of TRPV4 mRNA expression and the reduction of Ca2+ influx by the TRPV4 agonist GSK1016790A in TRPV4 siRNA-treated HTMC. TRPV4 siRNA-treated HTMC exhibited a significant reduction in Ca2+ influx and production of arachidonic acid and prostaglandin (PG) E2 induced by mechanical stretch, and direct activation of TRPV4 by GSK1016790A increased production of arachidonic acid, PGE2, and PGD2 and inhibited gel contraction. Furthermore, TRPV4-deficient mice had higher IOP than wild-type mice, and GSK1016790A administration lowered IOP. These results suggest that TRPV4 mediates the cellular response induced by trabecular meshwork stretch, leading to IOP reduction through the production of prostaglandins and inhibition of cell contraction. Targeting TRPV4 may have therapeutic benefits that lead to lowering IOP in glaucoma patients.
format article
author Takatoshi Uchida
Shota Shimizu
Reiko Yamagishi
Suzumi M Tokuoka
Yoshihiro Kita
Rei Sakata
Megumi Honjo
Makoto Aihara
author_facet Takatoshi Uchida
Shota Shimizu
Reiko Yamagishi
Suzumi M Tokuoka
Yoshihiro Kita
Rei Sakata
Megumi Honjo
Makoto Aihara
author_sort Takatoshi Uchida
title TRPV4 is activated by mechanical stimulation to induce prostaglandins release in trabecular meshwork, lowering intraocular pressure.
title_short TRPV4 is activated by mechanical stimulation to induce prostaglandins release in trabecular meshwork, lowering intraocular pressure.
title_full TRPV4 is activated by mechanical stimulation to induce prostaglandins release in trabecular meshwork, lowering intraocular pressure.
title_fullStr TRPV4 is activated by mechanical stimulation to induce prostaglandins release in trabecular meshwork, lowering intraocular pressure.
title_full_unstemmed TRPV4 is activated by mechanical stimulation to induce prostaglandins release in trabecular meshwork, lowering intraocular pressure.
title_sort trpv4 is activated by mechanical stimulation to induce prostaglandins release in trabecular meshwork, lowering intraocular pressure.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/8f21891e3fc246dcaaef2b5d7a54f8db
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