RGC Differentiation and Transplantation for NF-1 OPG

The optic neuropathy and vision loss seen in optic glioma (OPG) in some cases associated with neurofibromatosis type 1 (NF1) afflicts the eye and leads to damage and eventual loss of retinal ganglion cells (RGCs). Once lost, RGCs are not replaced in humans or other mammals resulting in irreversible blindness. Transplantation of stem cell-derived RGCs could be a feasible approach to restore vision; however, little is known about how to promote RGC differentiation from stem cells (SCs), or whether stem cell-derived RGCs transplanted into an adult would be able to integrate into either intact or degenerating retinal circuits. To date, several protocols have been reported for RGC generation from hiPSCs and hESCs, however these protocols are labor intensive, require significant time in culture, and yield only a few RGCs.

To overcome these issues, this project aims to utilize a rapid and direct induced RGC (iRGC) protocol modified from an induced neuron (iN) protocol established in an adjacent Stanford lab to investigate GDF, SoxC and other signaling on RGC fate specification in hiPSCs, with and without the NF1 background. The ultimate goal of this project will be to improve the efficiency of RGC differentiation from hiPSCs, and demonstrate efficacy of iRGC transplant with anatomic and functional assays, with attention to NF1 mutation in the donor iRGC population, and in the recipient host mouse.

Investigators

Jeffrey Goldberg, MD, PhD

Stanford University

School of Medicine

Jeffrey Goldberg, MD, PhD

Stanford University

School of Medicine

Current Stage

Discovery

Discovery
In Vivo Proof of Concept
IND Enabling
Clinical Trial Phase 1
Clinical Trial Phase 2
Clinical Trial Phase 3