Title of talk: Optic nerve regeneration: progress in animal models and strategies for translation

Talk abstract:
An estimated 80% of information about the outside world is normally transmitted to our brain from the retina via the optic nerve. Tragically, the mature optic nerve cannot regenerate if compromised, and retinal ganglion cells (RGCs), the projection neurons of the eye, soon begin to die. Using animal models, we discovered that sterile inflammation in the eye enables mature RGCs to regenerate axons through the injured optic nerve, and identified several previously unrecognized growth factors and their cognate receptors as the primary mediators of this phenomenon. Combined with complementary treatments, these factors enable some RGCs to regenerate axons from the eye to subcortical visual relay centers. Mechanistically, regenerative treatments activate a purine-sensitive protein kinase that initiates a downstream signaling cascade and culminates in a reversion of RGCs’ gene expression program to an earlier developmental stage. We have identified “master regulators” of the observed changes in gene expression, found that retinal interneurons gate RGCs’ ability to regenerate axons, and recently identified even stronger methods to promote optic nerve regeneration, including overexpression of a receptor that functions independently of a ligand. These findings and those from other labs will hopefully bring us closer to developing effective therapies for victims of traumatic, ischemic, and degenerative damage to the optic nerve.