Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 03, 2017
- Source ID
- 10.1073/pnas.1616811114
Entities
People
- Burcu Erdogan
- Christine Shrock
- Hui-ya Gilbert
- Kenya Yuki
- Kumiko Omura
- Larry Benowitz
- Lukas Andereggen
- Maria S. Asdourian
- Michal Hershfinkel
- Paul A. Rosenberg
- Silmara De Lima
- Stephen J. Lippard
- Ulf-peter Apfel
- Yehong Zhuo
- Yiqing Li
- Yuqin Yin
Organizations
- Adelson Foundation
- Alexander von Humboldt Foundation
- Ben-Gurion University of the Negev
- Boston Children's Hospital
- China Scholarship Council
- Harvard Medical School
- Kowa Life Science Foundation
- Massachusetts Institute of Technology
- National Eye Institute
- National Institute of General Medical Sciences
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke
- Sun Yat-sen University
- Swiss National Science Foundation
- United States Department of Defense