Abstract
Axons in the adult mammalian central nervous system (CNS) regenerate poorly after injury. Anatomically and developmentally, the retina is an extension of the CNS; it contains retinal ganglion cells (RGC), the axons of which form the optic nerve. The RGC axons are, therefore, CNS axons. A treatment that can protect RGC and promote optic nerve regeneration is critical for both acute and chronic optic nerve injury. We took advantage of optogenetic stimulation to specifically activate RGCs after injury, which increases the RGC survival rate, protects RGC unction, and promotes axon regeneration. We further identified the pathway that is activated by optogenetic stimulation; the IGF-1 pathway. IGF-1 is among the factors that are required for supporting the intrinsic axon growth of CNS neurons and IGF-1 absence severely impairs CNS axon growth. Finally, we demonstrate the application of 4-aminopyridine, a potassium channel blocker, can increase RGC responses to optogenetic stimulation, enhancing survival and axon regeneration. Collectively, these results illustrate the translational potential of optogenetic stimulation for adult RGC protection and optic nerve regeneration, which can be applied to preserve and even reverse vision loss.