{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:51:19Z","timestamp":1782978679335,"version":"3.54.5"},"reference-count":47,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,9,10]],"date-time":"2016-09-10T00:00:00Z","timestamp":1473465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"JSPS Grant-in-Aid for Scientific Research","award":["23592548"],"award-info":[{"award-number":["23592548"]}]}],"content-domain":{"domain":["heliyon.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Heliyon"],"published-print":{"date-parts":[[2016,10]]},"DOI":"10.1016\/j.heliyon.2016.e00191","type":"journal-article","created":{"date-parts":[[2016,10,28]],"date-time":"2016-10-28T14:30:46Z","timestamp":1477665046000},"page":"e00191","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":23,"title":["Effect of geranylgeranylacetone on the protection of retinal ganglion cells in a mouse model of normal tension glaucoma"],"prefix":"10.1016","volume":"2","author":[{"given":"Zhenyu","family":"Dong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Shinmei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saori","family":"Inafuku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Fukuhara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Ando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyoshi","family":"Kitaichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuhiro","family":"Kanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohichi","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kousuke","family":"Noda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Harada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinki","family":"Chin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Ishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.heliyon.2016.e00191_bib0005","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/35019501","article-title":"Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome","volume":"2","author":"Beere","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0010","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/00055735-200212000-00004","article-title":"Is normal tension glaucoma actually an unrecognized hereditary optic neuropathy? New evidence from genetic analysis","volume":"13","author":"Buono","year":"2002","journal-title":"Curr. Opin. Ophthalmol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0015","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.tcb.2008.01.007","article-title":"How do BCL-2 proteins induce mitochondrial outer membrane permeabilization?","volume":"18","author":"Chipuk","year":"2008","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0020","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/S0002-9394(98)00272-4","article-title":"The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma","volume":"126","author":"Collaborative Normal-Tension Glaucoma Study Group","year":"1998","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0025","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1097\/00007890-200107270-00003","article-title":"Geranylgeranylacetone a heat shock protein inducer, prevents primary graft nonfunction in rat liver transplantation","volume":"72","author":"Fudaba","year":"2001","journal-title":"Transplantation"},{"key":"10.1016\/j.heliyon.2016.e00191_bib0030","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1089\/neu.2006.23.1164","article-title":"Role of protein kinase C in neuroprotective effect of geranylgeranylacetone, a noninvasive inducing agent of heat shock protein, on delayed neuronal death caused by transient ischemia in rats","volume":"23","author":"Fujiki","year":"2006","journal-title":"J. Neurotrauma."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0035","doi-asserted-by":"crossref","first-page":"3333","DOI":"10.1167\/iovs.12-11256","article-title":"Reduction in blood glutathione levels occurs similarly in patients with primary-open angle or normal tension glaucoma","volume":"54","author":"Gherghel","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0040","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1001\/archopht.120.6.714","article-title":"The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma","volume":"120","author":"Gordon","year":"2002","journal-title":"Arch. Ophthalmol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0045","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/sj.cdd.4401369","article-title":"hsp70-DnaJ chaperone pair prevents nitric oxide- and CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondria","volume":"11","author":"Gotoh","year":"2004","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0050","doi-asserted-by":"crossref","first-page":"823","DOI":"10.3109\/02713683.2011.556299","article-title":"Evaluation of oxidative stress markers in aqueous humor of primary open angle glaucoma and primary angle closure glaucoma patients","volume":"39","author":"Goyal","year":"2014","journal-title":"Curr. Eye Res."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0055","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1038\/cdd.2010.62","article-title":"ASK1 deficiency attenuates neural cell death in GLAST-deficient mice: a model of normal tension glaucoma","volume":"17","author":"Harada","year":"2010","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0060","doi-asserted-by":"crossref","first-page":"261","DOI":"10.2353\/ajpath.2006.050765","article-title":"Role of apoptosis signal-regulating kinase 1 in stress-induced neural cell apoptosis in vivo","volume":"168","author":"Harada","year":"2006","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0065","first-page":"1601","article-title":"Neuroprotective effect of geranylgeranylacetone against ischemia-induced retinal injury","volume":"13","author":"Harada","year":"2007","journal-title":"Mol. Vis."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0070","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1172\/JCI30178","article-title":"The potential role of glutamate transporters in the pathogenesis of normal tension glaucoma","volume":"117","author":"Harada","year":"2007","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0075","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1167\/iovs.02-0912","article-title":"Retinal ganglion cell protection with geranylgeranylacetone a heat shock protein inducer, in a rat glaucoma model","volume":"44","author":"Ishii","year":"2003","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0080","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/0020-711X(91)90214-8","article-title":"The stress (heat shock) proteins","volume":"23","author":"Itoh","year":"1991","journal-title":"Int. J. Biochem."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0085","first-page":"1641","article-title":"The prevalence of primary open-angle glaucoma in Japanese: the Tajimi Study","volume":"111","author":"Iwase","year":"2004","journal-title":"Ophthalmology"},{"key":"10.1016\/j.heliyon.2016.e00191_bib0090","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1001\/archophthalmol.2010.20","article-title":"Delaying treatment of ocular hypertension: the ocular hypertension treatment study","volume":"128","author":"Kass","year":"2010","journal-title":"Arch. Ophthalmol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0095","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1006\/jmcc.2000.1250","article-title":"Cytoprotective mechanism of heat shock protein 70 against hypoxia\/reoxygenation injury","volume":"32","author":"Kawana","year":"2000","journal-title":"J. Mol. Cell. Cardiol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0100","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1016\/j.ajpath.2010.11.072","article-title":"Heat shock protein 70 (HSP70) is critical for the photoreceptor stress response after retinal detachment via modulating anti-apoptotic Akt kinase","volume":"178","author":"Kayama","year":"2011","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0105","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.neulet.2014.12.054","article-title":"Valproic acid prevents retinal degeneration in a murine model of normal tension glaucoma","volume":"588","author":"Kimura","year":"2015","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0110","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.imbio.2006.08.004","article-title":"Association of heat shock protein 70 induction and the amelioration of experimental autoimmune uveoretinitis in mice","volume":"212","author":"Kitamei","year":"2007","journal-title":"Immunobiology"},{"key":"10.1016\/j.heliyon.2016.e00191_bib0115","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0161-6420(97)30334-0","article-title":"Effect of trabeculectomy on visual field performance in central 30 degrees field in progressive normal-tension glaucoma","volume":"104","author":"Koseki","year":"1997","journal-title":"Ophthalmology"},{"key":"10.1016\/j.heliyon.2016.e00191_bib0120","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.3390\/ijms14012175","article-title":"Induction of heat shock protein 70 ameliorates ultraviolet-induced photokeratitis in mice","volume":"14","author":"Lennikov","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0125","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S0092-8674(00)80434-1","article-title":"Cytochrome c and dATP-dependent formation of Apaf-1\/caspase-9 complex initiates an apoptotic protease cascade","volume":"91","author":"Li","year":"1997","journal-title":"Cell"},{"key":"10.1016\/j.heliyon.2016.e00191_bib0130","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.heliyon.2016.e00191_bib0135","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/sj.jcbfm.9600080","article-title":"Hsp70 overexpression sequesters AIF and reduces neonatal hypoxic\/ischemic brain injury","volume":"25","author":"Matsumori","year":"2005","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0140","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1136\/bjo.80.10.864","article-title":"Twenty four hour blood pressure monitoring in normal tension glaucoma","volume":"80","author":"Meyer","year":"1996","journal-title":"Br. J. Ophthalmol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0145","doi-asserted-by":"crossref","first-page":"e00096","DOI":"10.1016\/j.heliyon.2016.e00096","article-title":"Neuroprotective effects of VCP modulators in mouse models of glaucoma","volume":"19","author":"Nakano","year":"2016","journal-title":"Heliyon"},{"key":"10.1016\/j.heliyon.2016.e00191_bib0150","doi-asserted-by":"crossref","first-page":"E51","DOI":"10.1038\/35055162","article-title":"Molecular chaperones and the art of recognizing a lost cause","volume":"3","author":"McClellan","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0155","first-page":"1940","article-title":"Concurrent downregulation of a glutamate transporter and receptor in glaucoma","volume":"41","author":"Naskar","year":"2000","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0160","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1161\/hc3901.095771","article-title":"Single oral dose of geranylgeranylacetone induces heat-shock protein 72 and renders protection against ischemia\/reperfusion injury in rat heart","volume":"104","author":"Ooie","year":"2001","journal-title":"Circulation"},{"key":"10.1016\/j.heliyon.2016.e00191_bib0165","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0079-6123(08)01124-2","article-title":"Pathogenesis of ganglion cell death in glaucoma and neuroprotection: focus on ganglion cell axonal mitochondria","volume":"173","author":"Osborne","year":"2008","journal-title":"Prog. Brain Res."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0170","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1093\/emboj\/20.3.446","article-title":"Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase","volume":"20","author":"Park","year":"2001","journal-title":"EMBO J."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0175","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The number of people with glaucoma worldwide in 2010 and 2020","volume":"90","author":"Quigley","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0180","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1002\/1531-8249(200006)47:6<782::AID-ANA11>3.0.CO;2-3","article-title":"Mice overexpressing rat heat shock protein 70 are protected against cerebral infarction","volume":"47","author":"Rajdev","year":"2000","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0185","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/ncb0901-839","article-title":"Heat-shock protein 70 antagonizes apoptosis-inducing factor","volume":"3","author":"Ravagnan","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0190","doi-asserted-by":"crossref","first-page":"17941","DOI":"10.1074\/jbc.274.25.17941","article-title":"Cytochrome c and dATP-mediated oligomerization of Apaf-1 is a prerequisite for procaspase-9 activation","volume":"274","author":"Saleh","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0195","doi-asserted-by":"crossref","first-page":"e1341","DOI":"10.1038\/cddis.2014.306","article-title":"Brimonidine prevents neurodegeneration in a mouse model of normal tension glaucoma","volume":"5","author":"Semba","year":"2014","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0200","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/S0161-6420(01)01009-0","article-title":"Long-term follow-up of visual field progression after trabeculectomy in progressive normal-tension glaucoma","volume":"109","author":"Shigeeda","year":"2002","journal-title":"Ophthalmology"},{"key":"10.1016\/j.heliyon.2016.e00191_bib0205","doi-asserted-by":"crossref","first-page":"38729","DOI":"10.1074\/jbc.M509497200","article-title":"Hsp70 inhibits heat-induced apoptosis upstream of mitochondria by preventing Bax translocation","volume":"280","author":"Stankiewicz","year":"2005","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0210","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S0002-9394(00)00538-9","article-title":"The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration","volume":"130","author":"The AGIS Investigators","year":"2000","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0215","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.brainres.2004.11.009","article-title":"Neuroprotective effect of a heat shock protein inducer: geranylgeranylacetone in permanent focal cerebral ischemia","volume":"1032","author":"Yasuda","year":"2005","journal-title":"Brain Res."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0220","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nrm2308","article-title":"The BCL-2 protein family: opposing activities that mediate cell death","volume":"9","author":"Youle","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0225","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/nrm1492","article-title":"Pathways of chaperone-mediated protein folding in the cytosol","volume":"5","author":"Young","year":"2004","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0230","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nrd3745","article-title":"Ophthalmic drug discovery: novel targets and mechanisms for retinal diseases and glaucoma","volume":"11","author":"Zhang","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.heliyon.2016.e00191_bib0235","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1161\/STROKEAHA.109.572537","article-title":"Recombinant Fv-Hsp70 protein mediates neuroprotection after focal cerebral ischemia in rats","volume":"41","author":"Zhan","year":"2010","journal-title":"Stroke"}],"container-title":["Heliyon"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2405844016313676?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2405844016313676?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,9,7]],"date-time":"2018-09-07T01:25:54Z","timestamp":1536283554000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2405844016313676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":47,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["S2405844016313676"],"URL":"https:\/\/doi.org\/10.1016\/j.heliyon.2016.e00191","relation":{},"ISSN":["2405-8440"],"issn-type":[{"value":"2405-8440","type":"print"}],"subject":[],"published":{"date-parts":[[2016,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Effect of geranylgeranylacetone on the protection of retinal ganglion cells in a mouse model of normal tension glaucoma","name":"articletitle","label":"Article Title"},{"value":"Heliyon","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.heliyon.2016.e00191","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"e00191"}}