Factors that Promote Ganglion Cell Regeneration

Currently, there are no effective therapies to replace degenerated neurons in patients with retinal ganglion cell loss from optic pathway glioma (OPG), such as occurs in patients with neurofibromatosis type 1 (NF1). By contrast, retinas of non-mammalian vertebrates, such as fish and amphibians, show a robust regenerative response following retinal damage. Upon injury to the retina, fish Müller Glia generate all different types of retinal neurons to replace those that were lost. There has been considerable progress in understanding the molecular mechanisms of regeneration in non-mammalian vertebrates, and if this knowledge could be applied to humans, it might lead to the development of new types of regenerative therapies for patients with impaired vision from neurofibromatosis type 1.

We have recently found that by expressing a key regulatory gene called Ascl1 in the Müller glia of mice, we can induce them to regenerate new neurons after injury to the ganglion cells. The new regenerated neurons in the mouse retinas wired up with the existing, undamaged neurons and became functional. These results showed for the first time that functional neuron regeneration is possible in mammals, like ourselves. However, not all types of retinal neurons have been successfully regenerated in the mouse retina, including the retinal ganglion cell which is lost in NF1 patients. In this project, we plan to figure out what is missing that would allow the Müller glia of mice to make new ganglion cells by developing novel screening methods to identify these factors. This includes a series of pilot experiments that will help ensure that the factors we identify in these screens are particularly relevant for NF1 patients.

Current Stage


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