PRESING

Abstract

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 PRESING (Piezo1 RESponsible for retinal INflammation in Glaucoma) project aims to identify the link between elevated IOP and the inflammatory response of microglia under glaucomatous conditions. We will elucidate the mechanisms triggered by Piezo1 activation in microglia when these cells are challenged with elevated pressure as well as the correlation with retinal ganglion cell loss. Moreover, an animal model of glaucoma with ocular hypertension in which Piezo1 will be deleted specifically in microglia will be used to clarify the involvement of Piezo1 channel in retinal neurodegeneration in glaucoma. We will employ several techniques and experimental models to provide evidence on the importance of Piezo1 ion channel activation in microglia following elevated pressure. We will evaluate the effects of elevated pressure on Piezo1 activation in microglia and the signaling mechanisms triggered by Piezo1 activation. In the retina, reactive microglia regulate immune cell infiltration, contributing to glaucoma pathogenesis. Therefore, the role of Piezo1 activation in antigen presentation by microglial cells and their interaction with CD4 T cells will be evaluated. Since retinal ganglion cells are lost in glaucoma and microglia reactivity has a key role, we will determine the effects of Piezo1 in microglia to the death of retinal ganglion cells. Then, we will use an animal model of glaucoma with ocular hypertension to study the contribution of microglial Piezo1 to glaucomatous neurodegeneration

In summary, PRESING will investigate the role of Piezo1 channel in microglia as the sensor of elevated pressure, leading to the inflammatory microglia response that contributes to the loss of retinal ganglion cells. The elucidation of early alterations in microglia may pave the way for the development of therapeutic strategies in glaucoma.