The role of Piezo1 in conventional aqueous humor outflow dynamics

Wei Zhu; Fei Hou; Jingwang Fang; Mohammad Reza Bahrani Fard; Yani Liu; Shouyan Ren; Shen Wu; Yunkun Qi; Shangru Sui; A Thomas Read; Joseph M Sherwood; Wei Zou; Hongxia Yu; Jingxue Zhang; Darryl R Overby; Ningli Wang; C Ross Ethier; KeWei Wang

doi:10.1016/j.isci.2021.102042

The role of Piezo1 in conventional aqueous humor outflow dynamics

iScience. 2021 Jan 7;24(2):102042. doi: 10.1016/j.isci.2021.102042. eCollection 2021 Feb 19.

Authors

Wei Zhu^{1

2}, Fei Hou^{1

3}, Jingwang Fang¹, Mohammad Reza Bahrani Fard⁴, Yani Liu¹, Shouyan Ren³, Shen Wu⁵, Yunkun Qi¹, Shangru Sui¹, A Thomas Read⁴, Joseph M Sherwood⁶, Wei Zou⁷, Hongxia Yu¹, Jingxue Zhang⁵, Darryl R Overby⁶, Ningli Wang⁵, C Ross Ethier^{4

8}, KeWei Wang^{1

9}

Affiliations

¹ Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, Shandong, China.
² Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University & Capital Medical University, Beijing 100730, China.
³ Department of Pharmacy, Affiliated Hospital of Qingdao University, Qingdao 266003, China.
⁴ George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta 30332, GA, USA.
⁵ Beijing Institute of Ophthalmology, Beijing Tongren Hospital Eye Center, Beijing 100730 China.
⁶ Department of Bioengineering, Imperial College London, London, UK.
⁷ School of Mechatronic Engineering, Jiangsu Normal University, Xuzhou 221116, China.
⁸ Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, 30332, GA, United States.
⁹ Institute of Innovative Drugs, Qingdao University, 38 Dengzhou Road, Qingdao 266021, Shandong, China.

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.

Keywords: Biomechanics; Cellular Physiology; Ophthalmology.