Piezo ion channels are a family of bona fide mechanically activated ion channels that play a crucial role in various biological processes by converting mechanical stimuli into electrical and chemical signals within cells. Discovered relatively recently, the family consists of Piezo1 and Piezo2, which are widely expressed across different tissues and cell types in vertebrates. Despite their broad expression, less is known regarding their roles and mechanisms in the visual system. This gap in knowledge presents a significant opportunity for research, particularly in understanding how these channels influence ocular functions and contribute to eye health and disease. We sought to interrogate the hypothesis that retinal ganglion cells (RGCs) express Piezo ion channels, enabling them to respond directly to mechanical strain, a critical factor in understanding their role in neurodegenerative diseases such as glaucoma. The research was structured around three specific aims designed to uncover the extent and implications of Piezo channel functionality in RGCs. The first aim focused on establishing whether Piezo ion channels are indeed expressed in RGCs, utilizing techniques such as semi-quantitative PCR and immunohistochemistry to detect the presence and quantify the levels of Piezo1 and potentially Piezo2 proteins and mRNA in the retina. This set the molecular groundwork for understanding mechanosensitivity in RGCs. The second aim validated the functionality of Piezo1 ion channel within RGCs using a pharmacological approach using a specific agonist of Piezo1 to monitor changes in RGC activity through calcium imaging and multi-electrode array recordings, assessing ion flux and changes in RGC firing in response to Piezo1 activation. This phase also explored whether the activation of Piezo1 which represents mechanical strains, highlighting the adaptive nature of RGCs to mechanical stress. The final aim was to develop and characterize a novel in vivo transgenic reporter mouse model, providing a tool for prolonged studies on how altered mechanosensitivity affects disease progression and recovery in RGCs. Together, these investigations provide significant insights into the mechanistic roles of Piezo channels in RGC biology and present potential new avenues for therapeutic intervention in ocular diseases marked by mechanical stress.