{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:57:59Z","timestamp":1791928679056,"version":"4.3.4"},"reference-count":32,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"10","license":[{"start":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T00:00:00Z","timestamp":1533081600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2018,8,1]]},"DOI":"10.1167\/iovs.18-23784","type":"journal-article","created":{"date-parts":[[2018,8,3]],"date-time":"2018-08-03T03:31:36Z","timestamp":1533267096000},"page":"3943","source":"Crossref","is-referenced-by-count":13,"title":["Ecel1 Knockdown With an AAV2-Mediated CRISPR\/Cas9 System Promotes Optic Nerve Damage-Induced RGC Death in the Mouse Retina"],"prefix":"10.1167","volume":"59","author":[{"given":"Kota","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan"},{"name":"Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihiro","family":"Shiga","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurika","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji M.","family":"Nishiguchi","sequence":"additional","affiliation":[{"name":"Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Tawarayama","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan"},{"name":"Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namie","family":"Murayama","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeto","family":"Maekawa","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Yabana","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuko","family":"Omodaka","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Katayama","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiwei","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Tsuda","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Nakazawa","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan"},{"name":"Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Miyagi, Japan"},{"name":"Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Miyagi, Japan"},{"name":"Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"i1552-5783-59-10-3943-b01","doi-asserted-by":"crossref","unstructured":"Sarkies N. Traumatic optic neuropathy. Eye (Lond). 2004; 18: 1122\u20131125.","DOI":"10.1038\/sj.eye.6701571"},{"key":"i1552-5783-59-10-3943-b02","doi-asserted-by":"crossref","unstructured":"Omodaka K, Horii T, Takahashi S, et al. 3D evaluation of the lamina cribrosa with swept-source optical coherence tomography in normal tension glaucoma. PLoS One. 2015; 10: e0122347.","DOI":"10.1371\/journal.pone.0122347"},{"key":"i1552-5783-59-10-3943-b03","doi-asserted-by":"crossref","unstructured":"Yasuda M, Tanaka Y, Ryu M, Tsuda S, Nakazawa T. RNA sequence reveals mouse retinal transcriptome changes early after axonal injury. PLoS One. 2014; 9: e93258.","DOI":"10.1371\/journal.pone.0093258"},{"key":"i1552-5783-59-10-3943-b04","doi-asserted-by":"crossref","unstructured":"Yasuda M, Tanaka Y, Omodaka K, et al. Transcriptome profiling of the rat retina after optic nerve transection. Sci Rep. 2016; 6: 28736.","DOI":"10.1038\/srep28736"},{"key":"i1552-5783-59-10-3943-b05","doi-asserted-by":"crossref","unstructured":"Kiryu-Seo S, Sasaki M, Yokohama H, et al. Damage-induced neuronal endopeptidase (DINE) is a unique metallopeptidase expressed in response to neuronal damage and activates superoxide scavengers. Proc Natl Acad Sci U S A. 2000; 97: 4345\u20134350.","DOI":"10.1073\/pnas.070509897"},{"key":"i1552-5783-59-10-3943-b06","doi-asserted-by":"crossref","unstructured":"Xu D, Emoto N, Giaid A, et al. ECE-1: a membrane-bound metalloprotease that catalyzes the proteolytic activation of big endothelin-1. Cell 1994; 78: 473\u2013485.","DOI":"10.1016\/0092-8674(94)90425-1"},{"key":"i1552-5783-59-10-3943-b07","doi-asserted-by":"crossref","unstructured":"Valdenaire O, Rohrbacher E, Langeveld A, Schweizer A, Meijers C. Organization and chromosomal localization of the human ECEL1 (XCE) gene encoding a zinc metallopeptidase involved in the nervous control of respiration. Biochem J. 2000; 346 (pt 3): 611\u2013616.","DOI":"10.1042\/bj3460611"},{"key":"i1552-5783-59-10-3943-b08","doi-asserted-by":"crossref","unstructured":"Benoit A, Vargas MA, Desgroseillers L, Boileau G. Endothelin-converting enzyme-like 1 (ECEL1) is present both in the plasma membrane and in the endoplasmic reticulum. Biochem J. 2004; 380: 881\u2013888.","DOI":"10.1042\/bj20040215"},{"key":"i1552-5783-59-10-3943-b09","doi-asserted-by":"crossref","unstructured":"Nagata K, Kiryu-Seo S, Kiyama H. Localization and ontogeny of damage-induced neuronal endopeptidase mRNA-expressing neurons in the rat nervous system. Neuroscience. 2006; 141: 299\u2013310.","DOI":"10.1016\/j.neuroscience.2006.03.032"},{"key":"i1552-5783-59-10-3943-b10","doi-asserted-by":"crossref","unstructured":"Schweizer A, Valdenaire O, Koster A, et al. Neonatal lethality in mice deficient in XCE, a novel member of the endothelin-converting enzyme and neutral endopeptidase family. J Biol Chem. 1999; 274: 20450\u201320456.","DOI":"10.1074\/jbc.274.29.20450"},{"key":"i1552-5783-59-10-3943-b11","doi-asserted-by":"crossref","unstructured":"Nagata K, Kiryu-Seo S, Maeda M, Yoshida K, Morita T, Kiyama H. Damage-induced neuronal endopeptidase is critical for presynaptic formation of neuromuscular junctions. J Neurosci. 2010; 30: 6954\u20136962.","DOI":"10.1523\/JNEUROSCI.4521-09.2010"},{"key":"i1552-5783-59-10-3943-b12","doi-asserted-by":"crossref","unstructured":"Matsumoto S, Kiryu-Seo S, Kiyama H. Motor nerve arborization requires proteolytic domain of damage-induced neuronal endopeptidase (DINE) during development. J Neurosci. 2016; 36: 4744\u20134757.","DOI":"10.1523\/JNEUROSCI.3811-15.2016"},{"key":"i1552-5783-59-10-3943-b13","doi-asserted-by":"crossref","unstructured":"Dieterich K, Quijano-Roy S, Monnier N, et al. The neuronal endopeptidase ECEL1 is associated with a distinct form of recessive distal arthrogryposis. Hum Mol Genet. 2013; 22: 1483\u20131492.","DOI":"10.1093\/hmg\/dds514"},{"key":"i1552-5783-59-10-3943-b14","doi-asserted-by":"crossref","unstructured":"McMillin MJ, Below JE, Shively KM, et al. Mutations in ECEL1 cause distal arthrogryposis type 5D. Am J Hum Genet. 2013; 92: 150\u2013156.","DOI":"10.1016\/j.ajhg.2012.11.014"},{"key":"i1552-5783-59-10-3943-b15","doi-asserted-by":"crossref","unstructured":"Nagata K, Kiryu-Seo S, Tamada H, Okuyama-Uchimura F, Kiyama H, Saido TC. ECEL1 mutation implicates impaired axonal arborization of motor nerves in the pathogenesis of distal arthrogryposis. Acta Neuropathol. 2016; 132: 111\u2013126.","DOI":"10.1007\/s00401-016-1554-0"},{"key":"i1552-5783-59-10-3943-b16","doi-asserted-by":"crossref","unstructured":"Kiryu-Seo S, Kato R, Ogawa T, Nakagomi S, Nagata K, Kiyama H. Neuronal injury-inducible gene is synergistically regulated by ATF3, c-Jun, and STAT3 through the interaction with Sp1 in damaged neurons. J Biol Chem. 2008; 283: 6988\u20136996.","DOI":"10.1074\/jbc.M707514200"},{"key":"i1552-5783-59-10-3943-b17","doi-asserted-by":"crossref","unstructured":"Kato R, Kiryu-Seo S, Kiyama H. Damage-induced neuronal endopeptidase (DINE\/ECEL) expression is regulated by leukemia inhibitory factor and deprivation of nerve growth factor in rat sensory ganglia after nerve injury. J Neurosci. 2002; 22: 9410\u20139418.","DOI":"10.1523\/JNEUROSCI.22-21-09410.2002"},{"key":"i1552-5783-59-10-3943-b18","doi-asserted-by":"crossref","unstructured":"Kiryu-Seo S, Kiyama H. The nuclear events guiding successful nerve regeneration. Front Mol Neurosci. 2011; 4: 53.","DOI":"10.3389\/fnmol.2011.00053"},{"key":"i1552-5783-59-10-3943-b19","doi-asserted-by":"crossref","unstructured":"Kaneko A, Kiryu-Seo S, Matsumoto S, Kiyama H. Damage-induced neuronal endopeptidase (DINE) enhances axonal regeneration potential of retinal ganglion cells after optic nerve injury. Cell Death Dis. 2017; 8: e2847.","DOI":"10.1038\/cddis.2017.212"},{"key":"i1552-5783-59-10-3943-b20","doi-asserted-by":"crossref","unstructured":"Ryu M, Yasuda M, Shi D, et al. Critical role of calpain in axonal damage-induced retinal ganglion cell death. J Neurosci Res. 2012; 90: 802\u2013815.","DOI":"10.1002\/jnr.22800"},{"key":"i1552-5783-59-10-3943-b21","doi-asserted-by":"crossref","unstructured":"Fujita K, Nishiguchi KM, Yokoyama Y, et al. In vivo cellular imaging of various stress\/response pathways using AAV following axonal injury in mice. Sci Rep. 2015; 5: 18141.","DOI":"10.1038\/srep18141"},{"key":"i1552-5783-59-10-3943-b22","doi-asserted-by":"crossref","unstructured":"Ivankovich AD, Miletich DJ, Reimann C, Albrecht RF, Zahed B. Cardiovascular effects of centrally administered ketamine in goats. Anesth Analg. 1974; 53: 924\u2013933.","DOI":"10.1213\/00000539-197453060-00022"},{"key":"i1552-5783-59-10-3943-b23","doi-asserted-by":"crossref","unstructured":"Newport DJ, Carpenter LL, McDonald WM, et al. Ketamine and Other NMDA antagonists: early clinical trials and possible mechanisms in depression. Am J Psychiatry. 2015; 172: 950\u2013966.","DOI":"10.1176\/appi.ajp.2015.15040465"},{"key":"i1552-5783-59-10-3943-b24","doi-asserted-by":"crossref","unstructured":"Nakazawa T, Takahashi H, Nishijima K, et al. Pitavastatin prevents NMDA-induced retinal ganglion cell death by suppressing leukocyte recruitment. J Neurochem. 2007; 100: 1018\u20131031.","DOI":"10.1111\/j.1471-4159.2006.04274.x"},{"key":"i1552-5783-59-10-3943-b25","doi-asserted-by":"crossref","unstructured":"Maekawa S, Sato K, Fujita K, et al. The neuroprotective effect of hesperidin in NMDA-induced retinal injury acts by suppressing oxidative stress and excessive calpain activation. Sci Rep. 2017; 7: 6885.","DOI":"10.1038\/s41598-017-06969-4"},{"key":"i1552-5783-59-10-3943-b26","doi-asserted-by":"crossref","unstructured":"Sato K, Li S, Gordon WC, et al. Receptor interacting protein kinase-mediated necrosis contributes to cone and rod photoreceptor degeneration in the retina lacking interphotoreceptor retinoid-binding protein. J Neurosci. 2013; 33: 17458\u201317468.","DOI":"10.1523\/JNEUROSCI.1380-13.2013"},{"key":"i1552-5783-59-10-3943-b27","doi-asserted-by":"crossref","unstructured":"Ran FA, Cong L, Yan WX, et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature. 2015; 520: 186\u2013191.","DOI":"10.1038\/nature14299"},{"key":"i1552-5783-59-10-3943-b28","doi-asserted-by":"crossref","unstructured":"Tsuda S, Tanaka Y, Kunikata H, et al. Real-time imaging of RGC death with a cell-impermeable nucleic acid dyeing compound after optic nerve crush in a murine model. Exp Eye Res. 2016; 146: 179\u2013188.","DOI":"10.1016\/j.exer.2016.03.017"},{"key":"i1552-5783-59-10-3943-b29","doi-asserted-by":"crossref","unstructured":"Kudo H, Nakazawa T, Shimura M, et al. Neuroprotective effect of latanoprost on rat retinal ganglion cells. Graefes Arch Clin Exp Ophthalmol. 2006; 244: 1003\u20131009.","DOI":"10.1007\/s00417-005-0215-0"},{"key":"i1552-5783-59-10-3943-b30","doi-asserted-by":"crossref","unstructured":"Hu Y, Park KK, Yang L, et al. Differential effects of unfolded protein response pathways on axon injury-induced death of retinal ganglion cells. Neuron. 2012; 73: 445\u2013452.","DOI":"10.1016\/j.neuron.2011.11.026"},{"key":"i1552-5783-59-10-3943-b31","doi-asserted-by":"crossref","unstructured":"Himori N, Yamamoto K, Maruyama K, et al. Critical role of Nrf2 in oxidative stress-induced retinal ganglion cell death. J Neurochem. 2013; 127: 669\u2013680.","DOI":"10.1111\/jnc.12325"},{"key":"i1552-5783-59-10-3943-b32","doi-asserted-by":"crossref","unstructured":"Agudo-Barriuso M, Lahoz A, Nadal-Nicolas FM, et al. Metabolomic changes in the rat retina after optic nerve crush. Invest Ophthalmol Vis Sci. 2013; 54: 4249\u20134259.","DOI":"10.1167\/iovs.12-11451"}],"container-title":["Investigative Opthalmology & Visual Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?articleid=2696449","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:30:56Z","timestamp":1791927056000},"score":1,"resource":{"primary":{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.18-23784"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,1]]},"references-count":32,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,8,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.18-23784","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2018,8,1]]}}}