Piezo 1 is involved in intraocular pressure regulation

Wataru Morozumi, Kota Aoshima, Satoshi Inagaki, Yuki Iwata, Shinsuke Nakamura, Hideaki Hara, Masamitsu Shimazawa
2021 Journal of Pharmacological Sciences  
17 18 J o u r n a l P r e -p r o o f ABSTRACT 1 Trabecular meshwork (TM) regulates the intraocular pressure (IOP) through the control 2 of aqueous humor outflow. Previous reports show that TM cells express 11 types of 3 mechanosensitive molecules, including Piezo 1, which sense mechanical stimuli. However, 4 the role of Piezo 1 on TM remains unclear. Thus, in this study, we focused on the Piezo 1 and 5 examined its role in TM cells. Immunostaining showed that Piezo 1 was expressed in mouse 6 TM
more » ... essed in mouse 6 TM and human TM cells. Moreover, the eye drops containing Piezo 1 agonist Yoda 1 reduced 7 the IOP in mice, and also reduced fibronectin expression level around the TM. In addition, 8 Piezo 1 activation suppressed human TM cells migration/proliferation, and decreased 9 fibronectin expression level. On the other hand, Piezo 1 activation increased matrix 10 metalloproteinase (MMP)-2 expression responsible for fibronectin degradation. These 11 findings could contribute to the development of new treatments for glaucoma. 12 13 Keywords 14 Piezo 1; glaucoma; trabecular meshwork; ECM; fibrosis 15 J o u r n a l P r e -p r o o f 1. INTRODUCTION 1 Glaucoma is a neurodegenerative disease that induces retinal ganglion cell (RGC) death 2 and leads to blindness 1 . Intraocular pressure (IOP) permanently changes according to balance 3 between production and outflow of aqueous humor (AH), and excessive AH production or 4 suppression of AH outflow causes high IOP 2 . Primary open angle glaucoma (POAG) is the 5 most common form of glaucoma and high IOP is important risk factor 3 . AH is discharged via 6 the trabecular meshwork (TM), or uveoscleral pathway 4,5 . The TM outflow pathway into the 7 Schlemm's canal (SC) is the main route of AH outflow 6 , and AH pass through the gap 8 between the trabecular meshwork cells and the extracellular matrix (ECM) 2,7 . Fibrosis of the 9 TM cells or ECM accumulation interferes with AH outflow and induces high IOP 8,9 . Actually, 10 in POAG patients, hindrance of AH outflow is often observed 10 . Previous reports indicate that 11 the number of TM cell are reduced, and TM produce excessive ECM in glaucoma patients 11,12 . 12 The effect of high IOP on optic nerve head is often studied, however, the effect of high IOP 13 on trabecular meshwork cells is still unclear. 14 Piezo is a mechanosensitive ion channel identified by Coste et al. in 2010 with two 15 subtypes Piezo 1/Fam 38A and Piezo 2/Fam 38B 13 . Piezo is a cation channel opened by 16 various mechanical stimuli such as pressure, shear stress, and extension of the cell membrane 17 14-16 . In addition, Yoda 1, an agonist of Piezo 1, binds to one of the three Piezo subunits, and 18 causes cation inflow by opening the channel 17 . Previous reports showed that Piezo 2 was 19
doi:10.1016/j.jphs.2021.06.005 fatcat:g6jzcnw7jbc6jl4bysnyy3zf5y