The role of mechanosensitive ion channel Piezo1 in glaucoma pathophysiology

Glaucoma is a neurodegenerative disease of the optic nerve and represents the leading cause of irreversible blindness worldwide. Elevated intraocular pressure represents the most significant and modifiable risk factor. However, in the retina, knowledge about how mechanical stimuli are sensed and modify neuron physiology remains unclear. Recent studies show that mechanosensitive ion channels are expressed in retina and may influence neurodegenerative processes. In our preliminary data, we discovered that activation of the mechanosensitive ion channel Piezo1 in retinal ganglion cells modulates cell survival after optic nerve injury. 

In this project, we will determine the role of activating and knocking out Piezo1 in a mouse model of glaucomatous injury. We will also determine the signaling pathways activated by Piezo1. Lastly, we will explore non-invasive methods of activating Piezo1 for clinical translation. 

Our research will increase our understanding of how the nervous system senses and responds to pressure, as well as the mechanisms mediating neuroprotection in pressure-mediated pathology. In addition, these studies will help us investigate mechanosensitive ion channel modulation as a promising therapeutic modality for glaucoma and other neurodegenerative diseases.