Regulation of intraocular pressure by microRNA cluster miR-143/145

Abstract Glaucoma is a major cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP), which causes optic nerve damage and retinal ganglion cell death, is the primary risk factor for blindness in glaucoma patients. IOP is controlled by the balance between aqueous humor secretio...

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Autores principales:	Xinyu Li, Fangkun Zhao, Mei Xin, Guorong Li, Coralia Luna, Guigang Li, Qinbo Zhou, Yuguang He, Bo Yu, Eric Olson, Pedro Gonzalez, Shusheng Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6f3cebbd698f4d089855f732aea18e72
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spelling	oai:doaj.org-article:6f3cebbd698f4d089855f732aea18e722021-12-02T15:05:36ZRegulation of intraocular pressure by microRNA cluster miR-143/14510.1038/s41598-017-01003-z2045-2322https://doaj.org/article/6f3cebbd698f4d089855f732aea18e722017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01003-zhttps://doaj.org/toc/2045-2322Abstract Glaucoma is a major cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP), which causes optic nerve damage and retinal ganglion cell death, is the primary risk factor for blindness in glaucoma patients. IOP is controlled by the balance between aqueous humor secretion from the ciliary body (CB) and its drainage through the trabecular meshwork (TM). How microRNAs (miRs) regulate IOP and glaucoma in vivo is largely unknown. Here we show that miR-143 and miR-145 expression is enriched in the smooth muscle and trabecular meshwork in the eye. Targeted deletion of miR-143/145 in mice results in significantly reduced IOP, consistent with an ~2-fold increase in outflow facilities. However, aqueous humor production in the same mice appears to be normal based on a microbeads-induced glaucoma model. Mechanistically, we found that miR-143/145 regulates actin dynamics and the contractility of TM cells, consistent with its regulation of actin-related protein complex (ARPC) subunit 2, 3, and 5, as well as myosin light chain kinase (MLCK) in these cells. Our data establish miR-143/145 as important regulators of IOP, which may have important therapeutic implications in glaucoma.Xinyu LiFangkun ZhaoMei XinGuorong LiCoralia LunaGuigang LiQinbo ZhouYuguang HeBo YuEric OlsonPedro GonzalezShusheng WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xinyu Li Fangkun Zhao Mei Xin Guorong Li Coralia Luna Guigang Li Qinbo Zhou Yuguang He Bo Yu Eric Olson Pedro Gonzalez Shusheng Wang Regulation of intraocular pressure by microRNA cluster miR-143/145
description	Abstract Glaucoma is a major cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP), which causes optic nerve damage and retinal ganglion cell death, is the primary risk factor for blindness in glaucoma patients. IOP is controlled by the balance between aqueous humor secretion from the ciliary body (CB) and its drainage through the trabecular meshwork (TM). How microRNAs (miRs) regulate IOP and glaucoma in vivo is largely unknown. Here we show that miR-143 and miR-145 expression is enriched in the smooth muscle and trabecular meshwork in the eye. Targeted deletion of miR-143/145 in mice results in significantly reduced IOP, consistent with an ~2-fold increase in outflow facilities. However, aqueous humor production in the same mice appears to be normal based on a microbeads-induced glaucoma model. Mechanistically, we found that miR-143/145 regulates actin dynamics and the contractility of TM cells, consistent with its regulation of actin-related protein complex (ARPC) subunit 2, 3, and 5, as well as myosin light chain kinase (MLCK) in these cells. Our data establish miR-143/145 as important regulators of IOP, which may have important therapeutic implications in glaucoma.
format	article
author	Xinyu Li Fangkun Zhao Mei Xin Guorong Li Coralia Luna Guigang Li Qinbo Zhou Yuguang He Bo Yu Eric Olson Pedro Gonzalez Shusheng Wang
author_facet	Xinyu Li Fangkun Zhao Mei Xin Guorong Li Coralia Luna Guigang Li Qinbo Zhou Yuguang He Bo Yu Eric Olson Pedro Gonzalez Shusheng Wang
author_sort	Xinyu Li
title	Regulation of intraocular pressure by microRNA cluster miR-143/145
title_short	Regulation of intraocular pressure by microRNA cluster miR-143/145
title_full	Regulation of intraocular pressure by microRNA cluster miR-143/145
title_fullStr	Regulation of intraocular pressure by microRNA cluster miR-143/145
title_full_unstemmed	Regulation of intraocular pressure by microRNA cluster miR-143/145
title_sort	regulation of intraocular pressure by microrna cluster mir-143/145
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6f3cebbd698f4d089855f732aea18e72
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Regulation of intraocular pressure by microRNA cluster miR-143/145

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