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
Affiliations
Wei Zhu
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, Shandong, China; Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University & Capital Medical University, Beijing 100730, China; Corresponding author
Fei Hou
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, Shandong, China; Department of Pharmacy, Affiliated Hospital of Qingdao University, Qingdao 266003, China
Jingwang Fang
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, Shandong, China
Mohammad Reza Bahrani Fard
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta 30332, GA, USA
Yani Liu
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, Shandong, China
Shouyan Ren
Department of Pharmacy, Affiliated Hospital of Qingdao University, Qingdao 266003, China
Shen Wu
Beijing Institute of Ophthalmology, Beijing Tongren Hospital Eye Center, Beijing 100730 China
Yunkun Qi
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, Shandong, China
Shangru Sui
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, Shandong, China
A. Thomas Read
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta 30332, GA, USA
Joseph M. Sherwood
Department of Bioengineering, Imperial College London, London, UK
Wei Zou
School of Mechatronic Engineering, Jiangsu Normal University, Xuzhou 221116, China
Hongxia Yu
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, Shandong, China
Jingxue Zhang
Beijing Institute of Ophthalmology, Beijing Tongren Hospital Eye Center, Beijing 100730 China
Darryl R. Overby
Department of Bioengineering, Imperial College London, London, UK
Ningli Wang
Beijing Institute of Ophthalmology, Beijing Tongren Hospital Eye Center, Beijing 100730 China
C. Ross Ethier
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta 30332, GA, USA; Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, 30332, GA, United States
KeWei Wang
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, Shandong, China; Institute of Innovative Drugs, Qingdao University, 38 Dengzhou Road, Qingdao 266021, Shandong, China; Corresponding author
Summary: 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.
