Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration
Name
Li-2017-Mobile zinc increases rapidly in the r.pdf
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Author(s)
Li, Yiqing
Andereggen, Lukas
Yuki, Kenya
Omura, Kumiko
Yin, Yuqin
Gilbert, Hui-Ya
Erdogan, Burcu
Asdourian, Maria S.
Shrock, Christine
de Lima, Silmara
Date Issued
January 2017
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Li, Yiqing et al. “Mobile Zinc Increases Rapidly in the Retina after Optic Nerve Injury and Regulates Ganglion Cell Survival and Optic Nerve Regeneration.” Proceedings of the National Academy of Sciences 114, 2 (January 2017): E209–E218 © 2017 National Academy of Sciences
Version
Final published version
Abstract
Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas RGC death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn²⁺) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn²⁺ increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to RGCs via vesicular release. Zn²⁺ accumulation in amacrine cell processes involves the Zn²⁺ transporter protein ZnT-3, and deletion of slc30a3, the gene encoding ZnT-3, promotes RGC survival and axon regeneration. Intravitreal injection of Zn²⁺ chelators enables many RGCs to survive for months after nerve injury and regenerate axons, and enhances the prosurvival and regenerative effects of deleting the gene for phosphatase and tensin homolog (pten). Importantly, the therapeutic window for Zn²⁺ chelation extends for several days after nerve injury. These results show that retinal Zn²⁺ dysregulation is a major factor limiting the survival and regenerative capacity of injured RGCs, and point to Zn²⁺ chelation as a strategy to promote long-term RGC protection and enhance axon regeneration.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1073/pnas.1616811114
