New tools for leveraging regenerative medicine to restore sight in glaucoma
ision restoration in glaucoma will require replacement of optic nerve neurons (RGCs), which die as a consequence of the disease. RGCs are the "relay neurons" of the eye, meaning that they directly communicate visual information from the eye to the brain, so connecting donor RGCs to the recipient retina is essential. Aim 1 develops an innovate reporter tool wherein donor RGCs will glow blue only after making functional connections to the host retina. Aim 2 develops a multicolor adaptive optics microscope capable of monitoring donor RGC engraftment into the host retina in living eyes.
Unlike traditional methods of studying connectivity between neurons, the approach designed here will: 1) allow study of many individual cells simultaneously; 2) label connected cells automatically and in real-time so that they can be tracked through imaging; 3) be applied to multiple different experimental model systems and species; 4) enable downstream studies of engrafted neurons and comparison to non-engrafted neurons.
This work will help bring RGC transplantation closer to human clinical trial for vision restoration in glaucoma and other optic neuropathies. We will broadly share the tools developed through this study to enable investigators to study synaptic connectivity of transplanted neurons in the retina (and in other parts of the central nervous system, like the brain and spinal cord) with high-throughput single-cell resolution. We hope that such work will enable clinical translation of neuronal transplantation to achieve functional recovery in multiple neurodegenerative disease.