A Novel Model for Replacing Lost Cells and Restoring Vision in Glaucoma Patients

Project Summary

Our project has two goals: 1) to identify genes required to regenerate the retinal cell type lost in glaucoma patients, “retinal ganglion cells” (RGCs), and 2) to establish new models for studying how specific subtypes of RGCs can be regenerated. To restore visual function to persons suffering with glaucoma, therapies are needed to replace lost RGCs. Although humans do not normally regenerate lost RGCs, our eyes do appear to retain a capacity to produce new neurons, suggesting an untapped potential for RGC regeneration. Unlike us, fish have a natural ability to replace lost retinal cells, including RGCs. In Aim 1, we will use a novel fish model of glaucoma and a large-scale genetic testing approach to identify genes that are required to regenerate RGCs, thus, to reveal strategies for promoting the eyes ability to repair itself. Recent evidence has emerged that specific subtypes of RGCs may be lost in glaucoma patients, necessitating studies into how discrete RGC subtypes can be replaced. In Aim 2, we will create novel fish models that enable, for the first time, exploration of mechanisms that regulate the replacement of specific RGC subtypes. As very little is currently known about RGC regeneration, our research program is well positioned to advance new knowledge. It is our hope that insights generated from the proposed studies will support the development of transformative regenerative therapies for restoring lost visual function to glaucoma patients.