Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration

Abstract

Significance The inability of CNS pathways to regenerate after injury can lead to devastating, life-long losses in sensory, motor, and other functions. We report that after injury to the optic nerve, a widely studied CNS pathway that normally cannot regenerate, mobile zinc (Zn 2+ ) increases rapidly in the processes of retinal interneurons (amacrine cells) and then transfers via vesicular release to retinal ganglion cells (RGCs), the injured projection neurons. Eliminating Zn 2+ leads to both persistent RGC survival and substantial axon regeneration with a broad therapeutic window. These findings show that signaling between interneurons and RGCs contributes to regulating the fate of RGCs after optic nerve injury, and that Zn 2+ chelation may provide a potent therapeutic approach.