The role of Piezo1 in conventional aqueous humor outflow dynamics

• Type of Material: Article
• Authors: Wei Zhu, Qingdao University; Fei Hou, Qingdao University; Jingwang Fang, Qingdao University; Mohammad Reza Bahrani Fard, Georgia Institute of Technology; Yani Liu, Qingdao University; Shouyan Ren, Qingdao University; Shen Wu, Beijing Tongren Hospital, Capital Medical University; Yunkun Qi, Qingdao University; Shangru Sui, Qingdao University; A. Thomas Read, Georgia Institute of Technology; Joseph M. Sherwood, Imperial College London; Wei Zou, Jiangsu Normal University; Hongxia Yu, Qingdao University; Jingxue Zhang, Beijing Tongren Hospital, Capital Medical University; Darryl R. Overby, Imperial College London; Ningli Wang, Beijing Tongren Hospital, Capital Medical University; Christopher Ethier, Emory University; KeWei Wang, Qingdao University
• Language: English
• Date: 2021-02-19
• Publisher: Cell Press
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.isci.2021.102042
• Title of Journal or Parent Work: iScience
• Volume: 24
• Issue: 2
• Start Page: 102042
• End Page: 102042
• Grant/Funding Information: Georgia Research Alliance; Shandong Province Shandong Province National Science Foundation ZR2017BH007, China; and Shandong Key Research and Development Program 2019GSF107075, China.; This study was supported by National Key Research and Development Program 2018YFA0109500; National Natural Science Foundation of China 81870653, 21807063, and 81730027
• Keywords: Stretch; Open-angle glaucoma; Intraoccular pressure; Stress; Mouse models; Science & Technology - Other Topics; Multidisciplinary Sciences; Target; Mechanosensitive; Activated ion channel; Science & Technology; Mechanotransduction; Trabecular meshwork cells
• Research Categories: Engineering, Biomedical; Health Sciences, Opthamology; Health Sciences, Immunology; Biology, Cell

Abstract

Controlling intraocular pressure (IOP) remains the mainstay of glaucoma therapy. The trabecular meshwork (TM), the key tissue responsible for aqueous humor (AH) outflow and IOP maintenance, is very sensitive to mechanical forces. However, it is not understood whether Piezo channels, very sensitive mechanosensors, functionally influence AH outflow. Here, we characterize the role of Piezo1 in conventional AH outflow. Immunostaining and western blot analysis showed that Piezo1 is widely expressed by TM. Patch-clamp recordings in TM cells confirmed the activation of Piezo1-derived mechanosensitive currents. Importantly, the antagonist GsMTx4 for mechanosensitive channels significantly decreased steady-state facility, yet activation of Piezo1 by the specific agonist Yoda1 did not lead to a facility change. Furthermore, GsMTx4, but not Yoda1, caused a significant increase in ocular compliance, a measure of the eye's transient response to IOP perturbation. Our findings demonstrate a potential role for Piezo1 in conventional outflow, likely under pathological and rapid transient conditions.