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

著者: Yiqing Li, Lukas Andereggen, Kenya Yuki, Kumiko Omura, Yuqin Yin, Hui-ya Gilbert, Burcu Erdoğan, Maria S. Asdourian, Christine Shrock, Silmara de Lima, Ulf‐Peter Apfel, Yehong Zhuo, Michal Hershfinkel, Stephen J. Lippard, Paul A. Rosenberg, Larry I. Benowitz - Proceedings of the National Academy of Sciences, PNAS 2017 被引用: 168

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.