Piezo 1 is involved in intraocular pressure regulation

J Pharmacol Sci. 2021 Oct;147(2):211-221. doi: 10.1016/j.jphs.2021.06.005. Epub 2021 Jun 19.

Abstract

Trabecular meshwork (TM) regulates the intraocular pressure (IOP) through the control of aqueous humor outflow. Previous reports show that TM cells express 11 types of mechanosensitive molecules, including Piezo 1, which sense mechanical stimuli. However, the role of Piezo 1 on TM remains unclear. Thus, in this study, we focused on the Piezo 1 and examined its role in TM cells. Immunostaining showed that Piezo 1 was expressed in mouse TM and human TM cells. Moreover, the eye drops containing Piezo 1 agonist Yoda 1 reduced the IOP in mice, and also reduced fibronectin expression level around the TM. In addition, Piezo 1 activation suppressed human TM cells migration/proliferation, and decreased fibronectin expression level. On the other hand, Piezo 1 activation increased matrix metalloproteinase (MMP)-2 expression responsible for fibronectin degradation. These findings could contribute to the development of new treatments for glaucoma.

Keywords: ECM; Fibrosis; Glaucoma; Piezo 1; Trabecular meshwork.

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Gene Expression / genetics*
  • Glaucoma / genetics*
  • Glaucoma / therapy*
  • Humans
  • Intraocular Pressure / genetics*
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Ion Channels / physiology*
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Mice
  • Mice, Inbred Strains
  • Molecular Targeted Therapy
  • Trabecular Meshwork / cytology
  • Trabecular Meshwork / metabolism

Substances

  • Fibronectins
  • Ion Channels
  • PIEZO1 protein, human
  • Piezo1 protein, mouse
  • Matrix Metalloproteinase 2