{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:58:46Z","timestamp":1791928726287,"version":"4.3.4"},"reference-count":56,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"12","license":[{"start":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T00:00:00Z","timestamp":1603670400000},"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":[[2020,10,26]]},"DOI":"10.1167\/iovs.61.12.23","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T11:30:57Z","timestamp":1603711857000},"page":"23","source":"Crossref","is-referenced-by-count":10,"title":["Down Syndrome Critical Region 1 Reduces Oxidative Stress\u2013Induced Retinal Ganglion Cells Apoptosis via CREB\u2013Bcl-2 Pathway"],"prefix":"10.1167","volume":"61","author":[{"given":"Yuxun","family":"Shi","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Department of Glaucoma, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Ye","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Department of Glaucoma, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Department of Glaucoma, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Department of Glaucoma, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Department of Glaucoma, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailiu","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Department of Glaucoma, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Department of Glaucoma, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"2647","DOI":"10.1172\/JCI91948","article-title":"Targeting neuronal gap junctions in mouse retina offers neuroprotection in glaucoma","volume":"127","author":"Akopian","year":"2017","journal-title":"J Clin Invest"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"3209","DOI":"10.1038\/s41467-018-05681-9","article-title":"Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma","volume":"9","author":"Chen","year":"2018","journal-title":"Nat Commun"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.coph.2012.09.008","article-title":"Oxidative stress and mitochondrial dysfunction in glaucoma","volume":"13","author":"Chrysostomou","year":"2013","journal-title":"Curr Opin Pharmacol"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1385\/MN:26:1","article-title":"Neurobiology of glaucomatous optic neuropathy: diverse cellular events in neurodegeneration and neuroprotection","volume":"26","author":"Wax","year":"2002","journal-title":"Mol Neurobiol"},{"issue":"suppl 1","key":"bib5","doi-asserted-by":"publisher","first-page":"S98","DOI":"10.1016\/S0039-6257(99)00027-2","article-title":"Direct and indirect approaches to neuroprotective therapy of glaucomatous optic neuropathy","volume":"43","author":"Levin","year":"1999","journal-title":"Surv Ophthalmol"},{"key":"bib6","article-title":"Regulator of calcineurin 1 is a novel RNA-binding protein to regulate neuronal apoptosis [published online ahead of print August 27, 2019]","author":"Yun","journal-title":"Mol Psychiatry"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/s41419-018-1299-x","article-title":"DAP5 increases axonal outgrowth of hippocampal neurons by enhancing the cap-independent translation of DSCR1.4 mRNA","volume":"10","author":"Seo","year":"2019","journal-title":"Cell Death Dis"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"10119","DOI":"10.1038\/ncomms10119","article-title":"RCAN1 links impaired neurotrophin trafficking to aberrant development of the sympathetic nervous system in Down syndrome","volume":"6","author":"Patel","year":"2015","journal-title":"Nat Commun"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"e47841","DOI":"10.1371\/journal.pone.0047841","article-title":"Over-expression of DSCR1 protects against post-ischemic neuronal injury","volume":"7","author":"Brait","year":"2012","journal-title":"PLoS One"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"6556","DOI":"10.1007\/s12035-016-0092-z","article-title":"Secretion of Down syndrome critical region 1 isoform 4 in ischemic retinal ganglion cells displays anti-angiogenic properties via NFATc1-dependent pathway","volume":"54","author":"Xu","year":"2017","journal-title":"Mol Neurobiol"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"9049","DOI":"10.1074\/jbc.M110.177519","article-title":"Regulator of calcineurin 1 (RCAN1) facilitates neuronal apoptosis through caspase-3 activation","volume":"286","author":"Sun","year":"2011","journal-title":"J Biol Chem"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"15794","DOI":"10.1073\/pnas.2536696100","article-title":"The Drosophila homolog of Down's syndrome critical region 1 gene regulates learning: implications for mental retardation","volume":"100","author":"Chang","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1007\/s12031-019-01309-9","article-title":"PACAP attenuates optic nerve crush-induced retinal ganglion cell apoptosis via activation of the CREB\u2013Bcl-2 pathway","volume":"68","author":"Ye","year":"2019","journal-title":"J Mol Neurosci"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1007\/s12031-018-1203-2","article-title":"Spatiotemporal expression changes of PACAP and its receptors in retinal ganglion cells after optic nerve crush","volume":"68","author":"Ye","year":"2019","journal-title":"J Mol Neurosci"},{"key":"bib15","first-page":"643","article-title":"Purification and culture of retinal ganglion cells from rodents","volume":"2013","author":"Winzeler","year":"2013","journal-title":"Cold Spring Harb Protoc"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"470","DOI":"10.3389\/fnmol.2018.00470","article-title":"Differences in gene expression profiles and phenotypes of differentiated SH-SY5Y neurons stably overexpressing mitochondrial ferritin","volume":"11","author":"Mendsaikhan","year":"2018","journal-title":"Front Mol Neurosci"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1111\/jpi.2006.41.issue-2","article-title":"Melatonin protects against hydrogen peroxide-induced cell death signaling in SH-SY5Y cultured cells: involvement of nuclear factor kappa B, Bax and Bcl-2","volume":"41","author":"Chetsawang","year":"2006","journal-title":"J Pineal Res"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"2880","DOI":"10.2353\/ajpath.2010.090853","article-title":"Expression of myocilin mutants sensitizes cells to oxidative stress-induced apoptosis: implication for glaucoma pathogenesis","volume":"176","author":"Joe","year":"2010","journal-title":"Am J Pathol"},{"key":"bib19","article-title":"Melatonin attenuates choroidal neovascularization by regulating macrophage\/microglia polarization via inhibition of RhoA\/ROCK signaling pathway [published online ahead of print April 22, 2020]","author":"Xu","journal-title":"J Pineal Res"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"e12473","DOI":"10.1111\/jpi.2018.64.issue-4","article-title":"Melatonin attenuated retinal neovascularization and neuroglial dysfunction by inhibition of HIF-1alpha-VEGF pathway in oxygen-induced retinopathy mice","volume":"64","author":"Xu","year":"2018","journal-title":"J Pineal Res"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1186\/s12974-015-0399-0","article-title":"Early pro-inflammatory cytokine elevations in the DBA\/2J mouse model of glaucoma","volume":"12","author":"Wilson","year":"2015","journal-title":"J Neuroinflammation"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1038\/s41419-018-0705-8","article-title":"Jnk2 deficiency increases the rate of glaucomatous neurodegeneration in ocular hypertensive DBA\/2J mice","volume":"9","author":"Harder","year":"2018","journal-title":"Cell Death Dis"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s13024-018-0303-3","article-title":"Inhibition of monocyte-like cell extravasation protects from neurodegeneration in DBA\/2J glaucoma","volume":"14","author":"Williams","year":"2019","journal-title":"Mol Neurodegener"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1007\/s12031-014-0332-5","article-title":"The expression changes of myelin and lymphocyte protein (MAL) following optic nerve crush in adult rats retinal ganglion cells","volume":"54","author":"Huang","year":"2014","journal-title":"J Mol Neurosci"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"72503","DOI":"10.18632\/oncotarget.v7i45","article-title":"Wogonin prevents TLR4-NF-kappaB-medicated neuro-inflammation and improves retinal ganglion cells survival in retina after optic nerve crush","volume":"7","author":"Xu","year":"2016","journal-title":"Oncotarget"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1002\/ptr.5036","article-title":"Curcumin I mediates neuroprotective effect through attenuation of quinoprotein formation, p-p38 MAPK expression, and caspase-3 activation in 6-hydroxydopamine treated SH-SY5Y cells","volume":"28","author":"Meesarapee","year":"2014","journal-title":"Phytother Res"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/BF03033267","article-title":"Expressions of caspase-3, Tunel, and Hsp72 immunoreactivities in cultured spinal cord neurons of rat after exposure to glutamate, nitric oxide, or peroxynitrite","volume":"3","author":"Manabe","year":"2001","journal-title":"Neurotox Res"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.nbd.2013.03.008","article-title":"Melatonin inhibits the caspase-1\/cytochrome c\/caspase-3 cell death pathway, inhibits MT1 receptor loss and delays disease progression in a mouse model of amyotrophic lateral sclerosis","volume":"55","author":"Zhang","year":"2013","journal-title":"Neurobiol Dis"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"24884","DOI":"10.1074\/jbc.273.38.24884","article-title":"CREB and its associated proteins act as survival factors for human melanoma cells","volume":"273","author":"Jean","year":"1998","journal-title":"J Biol Chem"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1146\/annurev.neuro.20.1.245","article-title":"Bcl-2 gene family in the nervous system","volume":"20","author":"Merry","year":"1997","journal-title":"Annu Rev Neurosci"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"27529","DOI":"10.1074\/jbc.274.39.27529","article-title":"Insulin-like growth factor-I induces bcl-2 promoter through the transcription factor cAMP-response element-binding protein","volume":"274","author":"Pugazhenthi","year":"1999","journal-title":"J Biol Chem"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"39859","DOI":"10.1074\/jbc.M112.384248","article-title":"Rit-mediated stress resistance involves a p38-mitogen- and stress-activated protein kinase 1 (MSK1)-dependent cAMP response element-binding protein (CREB) activation cascade","volume":"287","author":"Shi","year":"2012","journal-title":"J Biol Chem"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/1742-2094-9-48","article-title":"Regulator of calcineurin 1 (Rcan1) has a protective role in brain ischemia\/reperfusion injury","volume":"9","author":"Sobrado","year":"2012","journal-title":"J Neuroinflammation"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1101\/gad.1102703","article-title":"Transcriptional regulation by calcium, calcineurin, and NFAT","volume":"17","author":"Hogan","year":"2003","journal-title":"Genes Dev"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"39051","DOI":"10.1074\/jbc.M604659200","article-title":"Down syndrome candidate region 1 increases the stability of the IkappaBalpha protein: implications for its anti-inflammatory effects","volume":"281","author":"Kim","year":"2006","journal-title":"J Biol Chem"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1038\/nature08062","article-title":"Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1","volume":"459","author":"Baek","year":"2009","journal-title":"Nature"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"13161","DOI":"10.1523\/JNEUROSCI.3974-07.2007","article-title":"The Down syndrome critical region protein RCAN1 regulates long-term potentiation and memory via inhibition of phosphatase signaling","volume":"27","author":"Hoeffer","year":"2007","journal-title":"J Neurosci"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1002\/jcb.v114.5","article-title":"CREB-mediated Bcl-2 expression contributes to RCAN1 protection from hydrogen peroxide-induced neuronal death","volume":"114","author":"Kim","year":"2013","journal-title":"J Cell Biochem"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"37841","DOI":"10.1074\/jbc.M111.232165","article-title":"The regulator of calcineurin 1 (RCAN1\/DSCR1) activates the cAMP response element-binding protein (CREB) pathway","volume":"286","author":"Kim","year":"2011","journal-title":"J Biol Chem"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/j.exer.2010.09.001","article-title":"Loss of retinal function in aged DBA\/2J mice\u2014new insights into retinal neurodegeneration","volume":"91","author":"Heiduschka","year":"2010","journal-title":"Exp Eye Res"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1007\/s00401-003-0816-9","article-title":"Retinal neurodegeneration in the DBA\/2J mouse-a model for ocular hypertension","volume":"107","author":"Schuettauf","year":"2004","journal-title":"Acta Neuropathol"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"6059","DOI":"10.1167\/iovs.14-14421","article-title":"Loss of outer retinal neurons and circuitry alterations in the DBA\/2J mouse","volume":"55","author":"Fernandez-Sanchez","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1126\/science.aal0092","article-title":"Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice","volume":"355","author":"Williams","year":"2017","journal-title":"Science"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1002\/stem.2812","article-title":"Human periodontal ligament-derived stem cells promote retinal ganglion cell survival and axon regeneration after optic nerve injury","volume":"36","author":"Cen","year":"2018","journal-title":"Stem Cells"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1096\/fsb2.v16.8","article-title":"The DSCR1 (Adapt78) isoform 1 protein calcipressin 1 inhibits calcineurin and protects against acute calcium-mediated stress damage, including transient oxidative stress","volume":"16","author":"Ermak","year":"2002","journal-title":"FASEB J"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.devcel.2011.06.017","article-title":"Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics","volume":"21","author":"Martinou","year":"2011","journal-title":"Dev Cell"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.preteyeres.2011.11.002","article-title":"The molecular basis of retinal ganglion cell death in glaucoma","volume":"31","author":"Almasieh","year":"2012","journal-title":"Prog Retin Eye Res"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/jnc.2010.116.issue-1","article-title":"CREB: a multifaceted regulator of neuronal plasticity and protection","volume":"116","author":"Sakamoto","year":"2011","journal-title":"J Neurochem"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/S0896-6273(02)00686-4","article-title":"Apoptosis, axonal growth defects, and degeneration of peripheral neurons in mice lacking CREB","volume":"34","author":"Lonze","year":"2002","journal-title":"Neuron"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"346","DOI":"10.15252\/emmm.201505725","article-title":"Long non-coding RNA MALAT1 regulates retinal neurodegeneration through CREB signaling","volume":"8","author":"Yao","year":"2016","journal-title":"EMBO Mol Med"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s12031-013-0153-y","article-title":"Upregulation of CREM-1 relates to retinal ganglion cells apoptosis after light-induced damage in vivo","volume":"52","author":"Xu","year":"2014","journal-title":"J Mol Neurosci"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"5546","DOI":"10.1128\/MCB.16.10.5546","article-title":"Induction of bcl-2 expression by phosphorylated CREB proteins during B-cell activation and rescue from apoptosis","volume":"16","author":"Wilson","year":"1996","journal-title":"Mol Cell Biol"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1016\/j.febslet.2008.04.059","article-title":"CREB activates proteasomal degradation of DSCR1\/RCAN1","volume":"582","author":"Seo","year":"2008","journal-title":"FEBS Lett"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1073\/pnas.97.3.1020","article-title":"CBP\/p300 interact with and function as transcriptional coactivators of BRCA1","volume":"97","author":"Pao","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"7110","DOI":"10.1038\/sj.onc.1204890","article-title":"A CREB site in the BRCA1 proximal promoter acts as a constitutive transcriptional element","volume":"20","author":"Atlas","year":"2001","journal-title":"Oncogene"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"17418","DOI":"10.1073\/pnas.0704951104","article-title":"The SCFCdc4 ubiquitin ligase regulates calcineurin signaling through degradation of phosphorylated Rcn1, an inhibitor of calcineurin","volume":"104","author":"Kishi","year":"2007","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Investigative Opthalmology & Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2770948","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:16Z","timestamp":1791927076000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2770948"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,26]]},"references-count":56,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,10,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.61.12.23","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2020,10,26]]}}}