@article{bf26f14ee17a4ec19de19fd0591ec7c9,
title = "Preservation of vision after CaMKII-mediated protection of retinal ganglion cells",
abstract = "Retinal ganglion cells (RGCs) are the sole output neurons that transmit visual information from the retina to the brain. Diverse insults and pathological states cause degeneration of RGC somas and axons leading to irreversible vision loss. A fundamental question is whether manipulation of a key regulator of RGC survival can protect RGCs from diverse insults and pathological states, and ultimately preserve vision. Here, we report that CaMKII-CREB signaling is compromised after excitotoxic injury to RGC somas or optic nerve injury to RGC axons, and reactivation of this pathway robustly protects RGCs from both injuries. CaMKII activity also promotes RGC survival in the normal retina. Further, reactivation of CaMKII protects RGCs in two glaucoma models where RGCs degenerate from elevated intraocular pressure or genetic deficiency. Last, CaMKII reactivation protects long-distance RGC axon projections in vivo and preserves visual function, from the retina to the visual cortex, and visually guided behavior.",
keywords = "CREB, CaMKII, RGC, RGC protection, excitotoxicity, glaucoma, optic nerve crush, vision preservation, visual function, visual pathway",
author = "Xinzheng Guo and Jing Zhou and Christopher Starr and Mohns, {Ethan J.} and Yidong Li and Chen, {Earnest P.} and Yonejung Yoon and Kellner, {Christopher P.} and Kohichi Tanaka and Hongbing Wang and Wei Liu and Pasquale, {Louis R.} and Demb, {Jonathan B.} and Crair, {Michael C.} and Bo Chen",
note = "Funding Information: We thank Dr. Yang Hu (Stanford University) for providing AAV-mSncg-GFP plasmid and technical advice, Drs. Adriana Di Polo and Nicolas Belforte (University of Montreal) for technical help with the magnetic microbeads occlusion model, and the flow cytometry CoRE (Icahn School of Medicine at Mount Sinai) for technical help with RGC purification. This work was supported by National Institutes of Health grants R01 EY028921 , R01 EY024986 , R01 MH124992 , R01 EY015788 , P30 EY026878 , R01 EY022645 , R21 EY029806 , and R01 EY014454 ; an unrestricted challenge grant from Research to Prevent Blindness; and the McGraw Family Foundation for Vision Research . Funding Information: We thank Dr. Yang Hu (Stanford University) for providing AAV-mSncg-GFP plasmid and technical advice, Drs. Adriana Di Polo and Nicolas Belforte (University of Montreal) for technical help with the magnetic microbeads occlusion model, and the flow cytometry CoRE (Icahn School of Medicine at Mount Sinai) for technical help with RGC purification. This work was supported by National Institutes of Health grants R01 EY028921, R01 EY024986, R01 MH124992, R01 EY015788, P30 EY026878, R01 EY022645, R21 EY029806, and R01 EY014454; an unrestricted challenge grant from Research to Prevent Blindness; and the McGraw Family Foundation for Vision Research. X.G. conceived the project, designed and performed experiments, analyzed data, and wrote the paper. J.Z. designed and performed experiments. C.S. designed and performed experiments. E.J.M. Y.L. E.P.C. and Y.Y. performed experiments. C.K. K.T. H.W. W.L. L.R.P. J.B.D. and M.C.C. provided materials and expertise. B.C. conceived the project, designed experiments, analyzed data, supervised the project, and wrote the paper with instrumental input from J.B.D. All authors have read and approved the paper. B.C. and X.G. have filed a US patent application, 63/154,432, 63/177,230, based on the work in this paper. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = aug,
day = "5",
doi = "10.1016/j.cell.2021.06.031",
language = "English",
volume = "184",
pages = "4299--4314.e12",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "16",
}