The role of Piezo1 in conventional aqueous humor outflow dynamics.

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.

SUBMITTER: Zhu W 

PROVIDER: S-EPMC7829208 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature