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Investigation of associations between Piezo1 mechanoreceptor gain-of-function variants and glaucoma-related phenotypes in humans and mice
Glaucoma disproportionately affects individuals of African descent. Prior studies of the PIEZO1 mechanoreceptor have suggested a possible role in glaucoma pathophysiology. Here, we investigated associations between a Piezo1 gain-of-function variant common in individuals of African descent with glauc...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643131/ https://www.ncbi.nlm.nih.gov/pubmed/33149214 http://dx.doi.org/10.1038/s41598-020-76026-0 |
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author | Baxter, Sally L. Keenan, William T. Athanas, Argus J. Proudfoot, James A. Zangwill, Linda M. Ayyagari, Radha Liebmann, Jeffrey M. Girkin, Christopher A. Patapoutian, Ardem Weinreb, Robert N. |
author_facet | Baxter, Sally L. Keenan, William T. Athanas, Argus J. Proudfoot, James A. Zangwill, Linda M. Ayyagari, Radha Liebmann, Jeffrey M. Girkin, Christopher A. Patapoutian, Ardem Weinreb, Robert N. |
author_sort | Baxter, Sally L. |
collection | PubMed |
description | Glaucoma disproportionately affects individuals of African descent. Prior studies of the PIEZO1 mechanoreceptor have suggested a possible role in glaucoma pathophysiology. Here, we investigated associations between a Piezo1 gain-of-function variant common in individuals of African descent with glaucoma-related phenotypes. We analyzed whole genome sequences to identify Piezo1 variants and their frequencies among 1565 human participants. For the most common variant (e756del), we compared phenotypes between heterozygotes, homozygotes, and wildtypes. Longitudinal mixed effects models of visual field mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness were used to evaluate progression. Based on trends in the models, further investigation was conducted using Piezo1 gain-of-function mice. About 30% of African descent individuals had at least one e756del allele. There were trends suggesting e756del was associated with higher IOPs, thinner RNFLs, lower optic nerve head capillary densities, and greater decreases in MD and RNFL thickness over time, but these did not reach statistical significance. Among mice, increased Piezo1 activity was not significantly associated with IOP or retinal ganglion cell density. Our study confirms that the Piezo1 e756del gain-of-function variant is a frequent polymorphism present in African descent individuals but is unrelated to examined differences in glaucoma phenotypes. Ongoing work is needed to elucidate the role of Piezo1-mediated mechanotransduction in glaucoma. |
format | Online Article Text |
id | pubmed-7643131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-76431312020-11-06 Investigation of associations between Piezo1 mechanoreceptor gain-of-function variants and glaucoma-related phenotypes in humans and mice Baxter, Sally L. Keenan, William T. Athanas, Argus J. Proudfoot, James A. Zangwill, Linda M. Ayyagari, Radha Liebmann, Jeffrey M. Girkin, Christopher A. Patapoutian, Ardem Weinreb, Robert N. Sci Rep Article Glaucoma disproportionately affects individuals of African descent. Prior studies of the PIEZO1 mechanoreceptor have suggested a possible role in glaucoma pathophysiology. Here, we investigated associations between a Piezo1 gain-of-function variant common in individuals of African descent with glaucoma-related phenotypes. We analyzed whole genome sequences to identify Piezo1 variants and their frequencies among 1565 human participants. For the most common variant (e756del), we compared phenotypes between heterozygotes, homozygotes, and wildtypes. Longitudinal mixed effects models of visual field mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness were used to evaluate progression. Based on trends in the models, further investigation was conducted using Piezo1 gain-of-function mice. About 30% of African descent individuals had at least one e756del allele. There were trends suggesting e756del was associated with higher IOPs, thinner RNFLs, lower optic nerve head capillary densities, and greater decreases in MD and RNFL thickness over time, but these did not reach statistical significance. Among mice, increased Piezo1 activity was not significantly associated with IOP or retinal ganglion cell density. Our study confirms that the Piezo1 e756del gain-of-function variant is a frequent polymorphism present in African descent individuals but is unrelated to examined differences in glaucoma phenotypes. Ongoing work is needed to elucidate the role of Piezo1-mediated mechanotransduction in glaucoma. Nature Publishing Group UK 2020-11-04 /pmc/articles/PMC7643131/ /pubmed/33149214 http://dx.doi.org/10.1038/s41598-020-76026-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Baxter, Sally L. Keenan, William T. Athanas, Argus J. Proudfoot, James A. Zangwill, Linda M. Ayyagari, Radha Liebmann, Jeffrey M. Girkin, Christopher A. Patapoutian, Ardem Weinreb, Robert N. Investigation of associations between Piezo1 mechanoreceptor gain-of-function variants and glaucoma-related phenotypes in humans and mice |
title | Investigation of associations between Piezo1 mechanoreceptor gain-of-function variants and glaucoma-related phenotypes in humans and mice |
title_full | Investigation of associations between Piezo1 mechanoreceptor gain-of-function variants and glaucoma-related phenotypes in humans and mice |
title_fullStr | Investigation of associations between Piezo1 mechanoreceptor gain-of-function variants and glaucoma-related phenotypes in humans and mice |
title_full_unstemmed | Investigation of associations between Piezo1 mechanoreceptor gain-of-function variants and glaucoma-related phenotypes in humans and mice |
title_short | Investigation of associations between Piezo1 mechanoreceptor gain-of-function variants and glaucoma-related phenotypes in humans and mice |
title_sort | investigation of associations between piezo1 mechanoreceptor gain-of-function variants and glaucoma-related phenotypes in humans and mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643131/ https://www.ncbi.nlm.nih.gov/pubmed/33149214 http://dx.doi.org/10.1038/s41598-020-76026-0 |
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