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Piezo2 downregulation via the Cre-lox system affects aqueous humor dynamics in mice

PURPOSE: Proper aqueous humor (AH) dynamics is crucial for maintaining the intraocular pressure (IOP) in the eye. This study aims to investigate the function of Piezo2, a newly discovered mechanosensitive ion channel, in regulating AH dynamics. METHODS: Immunohistochemistry (IHC) analysis and wester...

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Autores principales: Fang, Jingwang, Hou, Fei, Wu, Shen, Liu, Yani, Wang, Linna, Zhang, Jingxue, Wang, Ningli, Wang, Kewei, Zhu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219506/
https://www.ncbi.nlm.nih.gov/pubmed/34220183
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author Fang, Jingwang
Hou, Fei
Wu, Shen
Liu, Yani
Wang, Linna
Zhang, Jingxue
Wang, Ningli
Wang, Kewei
Zhu, Wei
author_facet Fang, Jingwang
Hou, Fei
Wu, Shen
Liu, Yani
Wang, Linna
Zhang, Jingxue
Wang, Ningli
Wang, Kewei
Zhu, Wei
author_sort Fang, Jingwang
collection PubMed
description PURPOSE: Proper aqueous humor (AH) dynamics is crucial for maintaining the intraocular pressure (IOP) in the eye. This study aims to investigate the function of Piezo2, a newly discovered mechanosensitive ion channel, in regulating AH dynamics. METHODS: Immunohistochemistry (IHC) analysis and western blotting were performed to detect Piezo2 expression. The Cre-lox system was applied to create a conditional knockout model of Piezo2. IOP and aqueous humor outflow facility in live animals were recorded with a Tonometer and a syringe-pump system for up to 2 weeks. RESULTS: We first detected Piezo2 with robust expression in the human trabecular meshwork (TM), Schlemm’s canal (SC), the ciliary body’s epithelium, and ciliary muscle. In addition, we found Piezo2 in human retinal ganglion cells (RGCs) and astrocytes in the optic nerve head (ONH). Through the Cre-lox system, Piezo2 can be successfully downregulated in mouse iridocorneal angle tissues. However, Piezo2 downregulation cannot significantly influence the IOP and outflow facility through the conventional pathway. Instead, we observed an effect of downregulated Piezo2 on decreasing the intercept in the flow rate versus pressure plot. According to the Goldmann equation, Piezo2 may function in regulating unconventional outflow, AH production, and episcleral venous pressure. CONCLUSIONS: These findings, for the first time, demonstrate that Piezo2 acts as an essential mechanosensor in maintaining the proper aqueous humor dynamics in the eye.
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spelling pubmed-82195062021-07-02 Piezo2 downregulation via the Cre-lox system affects aqueous humor dynamics in mice Fang, Jingwang Hou, Fei Wu, Shen Liu, Yani Wang, Linna Zhang, Jingxue Wang, Ningli Wang, Kewei Zhu, Wei Mol Vis Research Article PURPOSE: Proper aqueous humor (AH) dynamics is crucial for maintaining the intraocular pressure (IOP) in the eye. This study aims to investigate the function of Piezo2, a newly discovered mechanosensitive ion channel, in regulating AH dynamics. METHODS: Immunohistochemistry (IHC) analysis and western blotting were performed to detect Piezo2 expression. The Cre-lox system was applied to create a conditional knockout model of Piezo2. IOP and aqueous humor outflow facility in live animals were recorded with a Tonometer and a syringe-pump system for up to 2 weeks. RESULTS: We first detected Piezo2 with robust expression in the human trabecular meshwork (TM), Schlemm’s canal (SC), the ciliary body’s epithelium, and ciliary muscle. In addition, we found Piezo2 in human retinal ganglion cells (RGCs) and astrocytes in the optic nerve head (ONH). Through the Cre-lox system, Piezo2 can be successfully downregulated in mouse iridocorneal angle tissues. However, Piezo2 downregulation cannot significantly influence the IOP and outflow facility through the conventional pathway. Instead, we observed an effect of downregulated Piezo2 on decreasing the intercept in the flow rate versus pressure plot. According to the Goldmann equation, Piezo2 may function in regulating unconventional outflow, AH production, and episcleral venous pressure. CONCLUSIONS: These findings, for the first time, demonstrate that Piezo2 acts as an essential mechanosensor in maintaining the proper aqueous humor dynamics in the eye. Molecular Vision 2021-05-20 /pmc/articles/PMC8219506/ /pubmed/34220183 Text en Copyright © 2021 Molecular Vision. https://creativecommons.org/licenses/by-nc-nd/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited, used for non-commercial purposes, and is not altered or transformed.
spellingShingle Research Article
Fang, Jingwang
Hou, Fei
Wu, Shen
Liu, Yani
Wang, Linna
Zhang, Jingxue
Wang, Ningli
Wang, Kewei
Zhu, Wei
Piezo2 downregulation via the Cre-lox system affects aqueous humor dynamics in mice
title Piezo2 downregulation via the Cre-lox system affects aqueous humor dynamics in mice
title_full Piezo2 downregulation via the Cre-lox system affects aqueous humor dynamics in mice
title_fullStr Piezo2 downregulation via the Cre-lox system affects aqueous humor dynamics in mice
title_full_unstemmed Piezo2 downregulation via the Cre-lox system affects aqueous humor dynamics in mice
title_short Piezo2 downregulation via the Cre-lox system affects aqueous humor dynamics in mice
title_sort piezo2 downregulation via the cre-lox system affects aqueous humor dynamics in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219506/
https://www.ncbi.nlm.nih.gov/pubmed/34220183
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