Deciphering the role of Piezo1 mechanosensitive channel in microglia-mediated glaucomatous neurodegeneration

Overview

Project Summary

Glaucoma, a leading cause of vision loss and global irreversible blindness, is a progressive chronic retinal neurodegenerative disease characterized by retinal ganglion cell loss and damage of the optic nerve (formed by retinal ganglion cell axons). Elevated intraocular pressure (IOP) and ageing are major risk factors for disease onset and progression. Glaucoma is a silent disease. It progresses without causing symptoms, delaying diagnosis until substantial amounts of neural damage. The pathophysiological mechanisms that contribute to glaucomatous neurodegeneration are not fully characterized. 

Chronic neuroinflammation mediated by microglial cells plays an important role in glaucoma pathogenesis, but the sensor in microglia for elevated pressure that triggers the inflammatory phenotype was not identified yet.

Piezo1 is a mechanosensitive ion channel that senses pressure and shearing stress and plays an important role in mechanotransduction. The project aims to identify the link between elevated IOP and the inflammatory response of microglia under glaucomatous conditions. 

Main Goals

The project will clarify the signalling mechanisms that link elevated IOP and retinal ganglion cell injury in glaucoma. Elucidating the mechanisms underlying microglia mechanosensing and its contribution to microglia phenotype will expand our understanding of how microglia contribute to neurodegeneration and has the potential to reveal novel therapeutic avenues for glaucoma.

Project Details