Investigation of associations between Piezo1 mechanoreceptor gain-of-function variants and glaucoma-related phenotypes in humans and mice View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-11-04

AUTHORS

Sally L. Baxter, William T. Keenan, Argus J. Athanas, James A. Proudfoot, Linda M. Zangwill, Radha Ayyagari, Jeffrey M. Liebmann, Christopher A. Girkin, Ardem Patapoutian, Robert N. Weinreb

ABSTRACT

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. More... »

PAGES

19013

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-020-76026-0

DOI

http://dx.doi.org/10.1038/s41598-020-76026-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1132295832

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33149214


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51 common variants
52 decrease
53 density
54 descent
55 descent individuals
56 deviation
57 differences
58 e756del allele
59 e756del gain
60 effects model
61 fiber layer thickness
62 field mean deviation
63 frequency
64 frequent polymorphisms
65 function mice
66 function variants
67 further investigation
68 gain
69 ganglion cell density
70 genome sequence
71 glaucoma
72 glaucoma pathophysiology
73 glaucoma phenotype
74 glaucoma-related phenotypes
75 greater decrease
76 head capillary densities
77 heterozygotes
78 high IOP
79 homozygotes
80 human participants
81 humans
82 individuals
83 investigation
84 investigation of associations
85 layer thickness
86 lower optic nerve head capillary densities
87 mean deviation
88 mechanoreceptor gain
89 mechanoreceptors
90 mechanotransduction
91 mice
92 mixed effects models
93 model
94 nerve fiber layer thickness
95 nerve head capillary densities
96 ongoing work
97 optic nerve head capillary densities
98 participants
99 pathophysiology
100 phenotype
101 polymorphism
102 possible role
103 prior studies
104 progression
105 retinal ganglion cell density
106 retinal nerve fiber layer thickness
107 role
108 sequence
109 significance
110 statistical significance
111 study
112 thickness
113 thinner RNFL
114 time
115 trends
116 variants
117 visual field mean deviation
118 whole genome sequences
119 wildtype
120 work
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