{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:59:01Z","timestamp":1790632741357,"version":"4.1.0"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T00:00:00Z","timestamp":1581552000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["H28C13, 17lm0203012h0001, and 18lm0203012h0002"],"award-info":[{"award-number":["H28C13, 17lm0203012h0001, and 18lm0203012h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Kyoto Drug Discovery & Development Co., Ltd."}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0229068","type":"journal-article","created":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T13:45:25Z","timestamp":1581601525000},"page":"e0229068","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Safety and effectiveness of a novel neuroprotectant, KUS121, in patients with non-arteritic central retinal artery occlusion: An open-label, non-randomized, first-in-humans, phase 1\/2 trial"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9572-8659","authenticated-orcid":true,"given":"Hanako Ohashi","family":"Ikeda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Muraoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Hata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriko","family":"Sumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyasu","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harue","family":"Tada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Kakizuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagahisa","family":"Yoshimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akitaka","family":"Tsujikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,2,13]]},"reference":[{"key":"pone.0229068.ref001","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1016\/j.ophtha.2014.04.029","article-title":"Nationwide incidence of clinically diagnosed central retinal artery occlusion in Korea, 2008 to 2011","volume":"121","author":"S Park","year":"2014","journal-title":"Ophthalmology"},{"key":"pone.0229068.ref002","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.ajo.2011.05.005","article-title":"The incidence of central retinal artery occlusion in Olmsted County, Minnesota","volume":"152","author":"JA Leavitt","year":"2011","journal-title":"Am J Ophthalmol"},{"key":"pone.0229068.ref003","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1159\/000050868","article-title":"The incidence of central retinal artery occlusion in the district of Split, Croatia","volume":"215","author":"M Ivanisevic","year":"2001","journal-title":"Ophthalmologica"},{"key":"pone.0229068.ref004","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/S0014-4835(03)00214-8","article-title":"Central retinal artery occlusion. Retinal survival time","volume":"78","author":"S Hayreh","year":"2004","journal-title":"Exp Eye Res"},{"key":"pone.0229068.ref005","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1136\/bjo.2006.097642","article-title":"Surgical embolus removal in retinal artery occlusion","volume":"90","author":"J Garcia-Arumi","year":"2006","journal-title":"Br J Ophthalmol"},{"key":"pone.0229068.ref006","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1007\/s00417-005-0140-2","article-title":"Multicenter study of the European Assessment Group for Lysis in the Eye (EAGLE) for the treatment of central retinal artery occlusion: design issues and implications. EAGLE Study report no. 1: EAGLE Study report no. 1","volume":"244","author":"N Feltgen","year":"2006","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"pone.0229068.ref007","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.ophtha.2010.03.061","article-title":"Central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment, a multicenter randomized trial","volume":"117","author":"M Schumacher","year":"2010","journal-title":"Ophthalmology"},{"key":"pone.0229068.ref008","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1161\/STROKEAHA.111.613653","article-title":"Efficacy of intravenous tissue-type plasminogen activator in central retinal artery occlusion: report from a randomized, controlled trial","volume":"42","author":"CS Chen","year":"2011","journal-title":"Stroke"},{"key":"pone.0229068.ref009","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1747-4949.2010.00545.x","article-title":"Study of the efficacy of intravenous tissue plasminogen activator in central retinal artery occlusion","volume":"6","author":"CS Chen","year":"2011","journal-title":"Int J Stroke"},{"key":"pone.0229068.ref010","first-page":"00043","article-title":"Evidence for an enduring ischaemic penumbra following central retinal artery occlusion, with implications for fibrinolytic therapy","volume":"22","author":"D McLeod","year":"2015","journal-title":"Prog Retin Eye Res"},{"key":"pone.0229068.ref011","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1001\/archopht.1968.03850040455014","article-title":"Experimental central retinal artery occlusion","volume":"79","author":"AJ Kroll","year":"1968","journal-title":"Arch Ophthalmol"},{"key":"pone.0229068.ref012","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1136\/bjo.50.6.325","article-title":"II. Ultrastructural changes in focal retinal ischaemia","volume":"50","author":"M Shakib","year":"1966","journal-title":"Br J Ophthalmol"},{"key":"pone.0229068.ref013","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.freeradbiomed.2011.12.013","article-title":"Effects of antioxidant gene therapy on retinal neurons and oxidative stress in a model of retinal ischemia\/reperfusion","volume":"52","author":"Y Liu","year":"2012","journal-title":"Free Radic Biol Med"},{"key":"pone.0229068.ref014","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.neulet.2014.05.042","article-title":"Down-regulation of GRP78 enhances apoptosis via CHOP pathway in retinal ischemia-reperfusion injury","volume":"575","author":"H Li","year":"2014","journal-title":"Neurosci Lett"},{"key":"pone.0229068.ref015","doi-asserted-by":"crossref","first-page":"5970","DOI":"10.1038\/srep05970","article-title":"Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosa","volume":"4","author":"HO Ikeda","year":"2014","journal-title":"Sci Rep"},{"key":"pone.0229068.ref016","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1042\/BST0360105","article-title":"Roles of VCP in human neurodegenerative disorders","volume":"36","author":"A. Kakizuka","year":"2008","journal-title":"Biochem Soc Trans"},{"key":"pone.0229068.ref017","doi-asserted-by":"crossref","first-page":"31184","DOI":"10.1038\/srep31184","article-title":"Neuroprotective efficacies by KUS121, a VCP modulator, on animal models of retinal degeneration","volume":"6","author":"T Hasegawa","year":"2016","journal-title":"Sci Rep"},{"key":"pone.0229068.ref018","doi-asserted-by":"crossref","first-page":"00096","DOI":"10.1016\/j.heliyon.2016.e00096","article-title":"Neuroprotective effects of VCP modulators in mouse models of glaucoma","volume":"2","author":"N Nakano","year":"2016","journal-title":"Heliyon"},{"key":"pone.0229068.ref019","doi-asserted-by":"crossref","first-page":"44873","DOI":"10.1038\/srep44873","article-title":"KUS121, a VCP modulator, attenuates ischemic retinal cell death via suppressing endoplasmic reticulum stress","volume":"7","author":"M Hata","year":"2017","journal-title":"Sci Rep"},{"key":"pone.0229068.ref020","doi-asserted-by":"crossref","first-page":"e00624","DOI":"10.1016\/j.heliyon.2018.e00624","article-title":"KUS121, an ATP regulator, mitigates chorioretinal pathologies in animal models of age-related macular degeneration","volume":"4","author":"Y Muraoka","year":"2018","journal-title":"Heliyon"},{"key":"pone.0229068.ref021","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1159\/000486145","article-title":"2018 Update on Intravitreal Injections: Euretina Expert Consensus Recommendations","volume":"239","author":"A Grzybowski","year":"2018","journal-title":"Ophthalmologica"},{"key":"pone.0229068.ref022","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0161-6420(99)00133-5","article-title":"Levodopa may improve vision loss in recent-onset, nonarteritic anterior ischemic optic neuropathy","volume":"107","author":"LN Johnson","year":"2000","journal-title":"Ophthalmology"},{"key":"pone.0229068.ref023","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.ajo.2005.03.038","article-title":"Central retinal artery occlusion: visual outcome","volume":"140","author":"S Hayreh","year":"2005","journal-title":"Am J Ophthalmol"},{"key":"pone.0229068.ref024","unstructured":"International Council of Ophthalmology. Visual Standards. Report prepared for the International Council of Ophthalmology at the 29th International Congress of Ophthalmology, Sydney, Australia, April 2002. Available at: http:\/\/www.icoph.org\/downloads\/visualstandardsreport.pdf. Date accessed: November 30, 2018"},{"key":"pone.0229068.ref025","volume-title":"Guides for the evaluation of permanent impairment. 5th edition","author":"AG Cocchiarella L","year":"2001"},{"key":"pone.0229068.ref026","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1001\/archopht.1968.03850040402007","article-title":"Grid for scoring visual fields. II. Perimeter","volume":"79","author":"B. Esterman","year":"1968","journal-title":"Arch Ophthalmol"},{"key":"pone.0229068.ref027","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1177\/112067211002000603","article-title":"Ocular neovascularization following central retinal artery occlusion: prevalence and timing of onset","volume":"20","author":"AK Rudkin","year":"2010","journal-title":"Eur J Ophthalmol"},{"key":"pone.0229068.ref028","doi-asserted-by":"crossref","first-page":"492","DOI":"10.5301\/ejo.5000033","article-title":"Localized foveal detachment in a patient with central retinal artery occlusion with cilioretinal sparing","volume":"22","author":"H Ozdemir","year":"2012","journal-title":"Eur J Ophthalmol"},{"key":"pone.0229068.ref029","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.ajo.2015.01.001","article-title":"Retinal and choroidal changes and visual outcome in central retinal artery occlusion: an optical coherence tomography study","volume":"159","author":"SJ Ahn","year":"2015","journal-title":"Am J Ophthalmol"},{"key":"pone.0229068.ref030","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1001\/jamaneurol.2015.1578","article-title":"Intravenous fibrinolytic therapy in central retinal artery occlusion: A patient-level meta-analysis","volume":"10","author":"M Schrag","year":"2015","journal-title":"JAMA Neurol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0229068","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T13:45:38Z","timestamp":1581601538000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0229068"}},"subtitle":[],"editor":[{"given":"Gianni","family":"Virgili","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,2,13]]},"references-count":30,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0229068","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,13]]}}}