Activation of Piezo 1 in the Pathogenesis of Glaucoma

Glaucoma is an eye disorder that damages the retinal ganglion cells and the optic nerve, and can cause vision loss or blindness. However, a lack of understanding of the underlying pathogenetic mechanisms has hampered the development of effective therapies. The aim of this report was to investigate the potential role of Piezo 1 in glaucoma development, by using a bead injection-based animal model of glaucoma. Piezo 1 expression was not significantly altered by ocular hypertension in both whole eyeballs and the retina in glaucomatous eyes. Moreover, no marked differences in β-actin expression were observed between glaucomatous eyes and normal eyes. Nevertheless, enhanced expression of Cofilin, a downstream target of the Yap/Piezo 1 signaling pathway, not only accelerated depolymerization of F-actin to G-actin but also enhanced retinal cell calcium concentrations in glaucomatous eyes. The development of glaucoma in bead-injected eyes was almost completely abrogated by administration of the Piezo 1 inhibitor GsMTx-TFA. Together, these results suggested that activation of Piezo 1 might be crucial for the initiation of glaucomatous injury, by increasing calcium concentrations in retinal cells, leading to up-regulation of Cofilin expression, accelerating depolymerization of F-actin to G-actin, and ultimately disrupting the actin dynamic balance between G-actin and F-actin.