Our overall goal in this project is to improve the success of RGC transplantation, using mouse cells, together with tissue engineering and pig-to-pig transplantation studies. It is important to first identify and optimize key variables using mouse cells that can be applied for pig, non-human primate, and human retinal ganglion cell precursors. We have previously shown that mouse stem cells-derived RGCs are diverse, functional and integrate into healthy and RGC-depleted retinas following injection into the chamber of the eye in front of the retina. We have also demonstrated long-term survival and growth of processes into the optic nerve.
We have three sub-aims for this approach: 1) Identifying the stage of differentiation with the highest potential for transplantation, 2) Evaluating different types of RGCs for transplantation studies, and 3) Improving RGC maturation in retinal tissue, differentiated from stem cells. We will work closely with team members to develop appropriate differentiation and transplantation protocols. We will also develop novel tissue engineered transplants aimed at improving graft success. Using cells and protocols from Aim 1, we will develop polymer composite grafts capable of improving survival, engraftment, and differentiation of transplanted RGCs. Cells from other VRI collaborators, along with cells from Aim 1, will be used for these studies. Lastly, building upon studies by team members using mouse and human RGCs, we will develop pig RGCs for the purpose of performing pig-pig allograft (same species) studies in disease models using protocols generated by other Dream Team members.