Nfe2l3-regulated mechanisms of retinal ganglion cell neuroprotection and optic nerve axon regeneration

About This Grant

Project Summary The molecular mechanisms controlling the growth of axonal projections in the central nervous system (CNS) are still poorly understood. Similarly, the molecular basis of the failure of axon regeneration in the CNS are still elusive, and no regenerative therapies exist to date that could help patients with axonal injuries. Retinal ganglion cells (RGCs) are prototypical CNS projection neurons that do not spontaneously regenerate axons disrupted in optic neuropathies caused by trauma, ischemia, or glaucoma, resulting in irreversible loss of vision. Our goal is to investigate the molecular mechanisms through which the Nfe2l3 protein, whose neuroprotective functions we recently identified, regulates the regeneration process of the damaged optic nerve axons, and to test their potential for restoring simple visual functions after optic nerve injury. We will utilize established animal models and state-of-the-art technologies for investigating through which molecular mechanism the Nfe2l3 protein activates the retinal ganglion cells’ intrinsic capacity for regenerating long-distance axons through the optic nerve. We will also determine which retinal ganglion cells respond to the Nfe2l3 protein by regenerating injured axons. We expect that these studies will lead to the development of a novel approach for restoring simple visual functions after optic nerve injury, with the potential to treat different types of optic neuropathies.