@article {987996,
	title = {Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {114},
	number = {2},
	year = {2017},
	pages = {E209-E218},
	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 (Zn(2+)) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn(2+) increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to RGCs via vesicular release. Zn(2+) accumulation in amacrine cell processes involves the Zn(2+) transporter protein ZnT-3, and deletion of slc30a3, the gene encoding ZnT-3, promotes RGC survival and axon regeneration. Intravitreal injection of Zn(2+) 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 Zn(2+) chelation extends for several days after nerve injury. These results show that retinal Zn(2+) dysregulation is a major factor limiting the survival and regenerative capacity of injured RGCs, and point to Zn(2+) chelation as a strategy to promote long-term RGC protection and enhance axon regeneration.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1616811114},
	author = {Li, Yiqing and Andereggen, Lukas and Yuki, Kenya and Omura, Kumiko and Yin, Yuqin and Gilbert, Hui-Ya and Erdogan, Burcu and Asdourian, Maria S and Shrock, Christine and de Lima, Silmara and Apfel, Ulf-Peter and Zhuo, Yehong and Hershfinkel, Michal and Lippard, Stephen J and Rosenberg, Paul A and Benowitz, Larry}
}
