It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
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.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details
1 University of California San Diego (UCSD), Hamilton Glaucoma Center, Viterbi Family Department of Ophthalmology, and Shiley Eye Institute, La Jolla, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242); UCSD, Health Department of Biomedical Informatics, La Jolla, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242)
2 Scripps Research Institute, La Jolla, USA (GRID:grid.214007.0) (ISNI:0000000122199231)
3 UCSD, Health Department of Biomedical Informatics, La Jolla, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242)
4 University of California San Diego (UCSD), Hamilton Glaucoma Center, Viterbi Family Department of Ophthalmology, and Shiley Eye Institute, La Jolla, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242)
5 Columbia University Irving Medical Center, Bernard and Shirlee Brown Glaucoma Research Laboratory, Edward S. Harkness Eye Institute, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729)
6 University of Alabama at Birmingham, Department of Ophthalmology and Vision Sciences, Callahan Eye Hospital, Birmingham, USA (GRID:grid.265892.2) (ISNI:0000000106344187)