{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:59:18Z","timestamp":1791928758979,"version":"4.3.4"},"reference-count":37,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"13","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"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":[[2021,10,26]]},"DOI":"10.1167\/iovs.62.13.23","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T11:49:13Z","timestamp":1635248953000},"page":"23","source":"Crossref","is-referenced-by-count":13,"title":["Apolipoprotein E-Containing Lipoproteins and LRP1 Protect From NMDA-Induced Excitotoxicity Associated With Reducing \u03b12-Macroglobulin in M\u00fcller Glia"],"prefix":"10.1167","volume":"62","author":[{"given":"Hideki","family":"Hayashi","sequence":"first","affiliation":[{"name":"Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misuzu","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Harashima","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Hashizume","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Furiya","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihaya","family":"Mukaigaito","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Takemura","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Mise","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yuan","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, School of Pharmacy, Josai University, Sakado, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Takagi","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1016\/S0140-6736(17)31469-1","article-title":"Glaucoma","volume":"390","author":"Jonas","year":"2017","journal-title":"Lancet"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1038\/s41433-018-0042-2","article-title":"Normal tension glaucoma: review of current understanding and mechanisms of the pathogenesis","volume":"32","author":"Killer","year":"2018","journal-title":"Eye (Lond)"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"874","DOI":"10.3390\/antiox9090874","article-title":"Suppression of Oxidative Stress as Potential Therapeutic Approach for Normal Tension Glaucoma","volume":"9","author":"Harada","year":"2020","journal-title":"Antioxidants (Basel)"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/bs.pbr.2015.05.007","article-title":"Advance in the pathogenesis and treatment of normal-tension glaucoma","volume":"221","author":"Mastropasqua","year":"2015","journal-title":"Prog Brain Res"},{"key":"bib5","doi-asserted-by":"publisher","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":"bib6","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1136\/bjophthalmol-2018-312724","article-title":"Recent advances in genetically modified animal models of glaucoma and their roles in drug repositioning","volume":"103","author":"Harada","year":"2019","journal-title":"Br J Ophthalmol"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"3862","DOI":"10.1074\/jbc.M309475200","article-title":"Astroglial regulation of apolipoprotein E expression in neuronal cells. Implications for Alzheimer's disease","volume":"279","author":"Harris","year":"2004","journal-title":"J Biol Chem"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1161\/ATVBAHA.116.307023","article-title":"Central Nervous System Lipoproteins: ApoE and Regulation of Cholesterol Metabolism","volume":"36","author":"Mahley","year":"2016","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"2645","DOI":"10.1002\/jnr.v87:12","article-title":"Activated retinal glia promote neurite outgrowth of retinal ganglion cells via apolipoprotein E","volume":"87","author":"Lorber","year":"2009","journal-title":"J Neurosci Res"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1006\/exnr.1995.1088","article-title":"Neurodegeneration in the central nervous system of apoE-deficient mice","volume":"136","author":"Masliah","year":"1995","journal-title":"Exp Neurol"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1161\/01.STR.30.5.1118","article-title":"Apolipoprotein E deficiency worsens outcome from global cerebral ischemia in the mouse","volume":"30","author":"Sheng","year":"1999","journal-title":"Stroke"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.neuint.2009.01.010","article-title":"Apolipoprotein E-deficient mice are more vulnerable to ER stress after transient forebrain ischemia","volume":"54","author":"Osada","year":"2009","journal-title":"Neurochem Int"},{"key":"bib13","doi-asserted-by":"crossref","first-page":"a006312","DOI":"10.1101\/cshperspect.a006312","article-title":"Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease","volume":"2","author":"Holtzman","year":"2012","journal-title":"Cold Spring Harb Perspect Med"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"571","DOI":"10.3390\/ijms20030571","article-title":"Dual Roles of Astrocyte-Derived Factors in Regulation of Blood-Brain Barrier Function after Brain Damage","volume":"20","author":"Michinaga","year":"2019","journal-title":"Int J Mol Sci"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.1523\/JNEUROSCI.5471-06.2007","article-title":"Apolipoprotein E-containing lipoproteins protect neurons from apoptosis via a signaling pathway involving low-density lipoprotein receptor-related protein-1","volume":"27","author":"Hayashi","year":"2007","journal-title":"J Neurosci"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"29605","DOI":"10.1074\/jbc.M109.039560","article-title":"Protection of neurons from apoptosis by apolipoprotein E-containing lipoproteins does not require lipoprotein uptake and involves activation of phospholipase Cgamma1 and inhibition of calcineurin","volume":"284","author":"Hayashi","year":"2009","journal-title":"J Biol Chem"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"25395","DOI":"10.1074\/jbc.M112.370130","article-title":"A potential neuroprotective role of apolipoprotein E-containing lipoproteins through low density lipoprotein receptor-related protein 1 in normal tension glaucoma","volume":"287","author":"Hayashi","year":"2012","journal-title":"J Biol Chem"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"5410657","DOI":"10.1155\/2019\/5410657","article-title":"Alpha-2-Macroglobulin, a Hypochlorite-Regulated Chaperone and Immune System Modulator","volume":"2019","author":"Cater","year":"2019","journal-title":"Oxid Med Cell Longev"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"29156","DOI":"10.1074\/jbc.M802365200","article-title":"Alpha2-macroglobulin is a mediator of retinal ganglion cell death in glaucoma","volume":"283","author":"Shi","year":"2008","journal-title":"J Biol Chem"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"5353","DOI":"10.1167\/iovs.13-12245","article-title":"Elevated levels of multiple biomarkers of Alzheimer's disease in the aqueous humor of eyes with open-angle glaucoma","volume":"54","author":"Inoue","year":"2013","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.abb.2018.04.010","article-title":"Biological activities of laminin-111-derived peptide-chitosan matrices in a primary culture of rat cortical neurons","volume":"648","author":"Hayashi","year":"2018","journal-title":"Arch Biochem Biophys"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"581915","DOI":"10.3389\/fnins.2020.581915","article-title":"Investigating the Relationship Between Neuronal Cell Death and Early DNA Methylation After Ischemic Injury","volume":"14","author":"Asada","year":"2020","journal-title":"Front Neurosci"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"6461","DOI":"10.1167\/iovs.16-19494","article-title":"Potential Neuroprotective Effects of an LSD1 Inhibitor in Retinal Ganglion Cells via p38 MAPK Activity","volume":"57","author":"Tsutsumi","year":"2016","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/S0145-305X(99)00018-X","article-title":"Alpha2-macroglobulin: an evolutionarily conserved arm of the innate immune system","volume":"23","author":"Armstrong","year":"1999","journal-title":"Dev Comp Immunol"},{"key":"bib25","first-page":"819","article-title":"Retrograde labeling of retinal ganglion cells by application of fluoro-gold on the surface of superior colliculus","volume":"16","author":"Chiu","year":"2008","journal-title":"J Vis Exp"},{"issue":"Suppl 1","key":"bib26","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1016\/S0039-6257(03)00008-0","article-title":"Possible role for memantine in protecting retinal ganglion cells from glaucomatous damage","volume":"48","author":"Lipton","year":"2003","journal-title":"Surv Ophthalmol"},{"key":"bib27","doi-asserted-by":"crossref","first-page":"5743109","DOI":"10.1155\/2019\/5743109","article-title":"Cellular Signaling in Muller Glia: Progenitor Cells for Regenerative and Neuroprotective Responses in Pharmacological Models of Retinal Degeneration","volume":"2019","author":"Liu","year":"2019","journal-title":"J Ophthalmol"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"5260","DOI":"10.1167\/iovs.10-6691","article-title":"During glaucoma, alpha2-macroglobulin accumulates in aqueous humor and binds to nerve growth factor, neutralizing neuroprotection","volume":"52","author":"Bai","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.exer.2007.07.018","article-title":"Effect of retinal laser photocoagulation on the activity of metalloproteinases and the alpha(2)-macroglobulin proteolytic state in the vitreous of eyes with proliferative diabetic retinopathy","volume":"85","author":"Sanchez","year":"2007","journal-title":"Exp Eye Res"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1111\/nyas.2002.977.issue-1","article-title":"Neuroprotective effect of apolipoprotein E against ischemia","volume":"977","author":"Kitagawa","year":"2002","journal-title":"Ann N Y Acad Sci"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.expneurol.2017.10.014","article-title":"Apolipoprotein E as a novel therapeutic neuroprotection target after traumatic spinal cord injury","volume":"299","author":"Cheng","year":"2018","journal-title":"Exp Neurol"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"3181","DOI":"10.1096\/fsb2.v27.8","article-title":"Activated alpha2-macroglobulin induces Muller glial cell migration by regulating MT1-MMP activity through LRP1","volume":"27","author":"Barcelona","year":"2013","journal-title":"FASEB J"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1167\/iovs.10-5759","article-title":"alpha2-Macroglobulin induces glial fibrillary acidic protein expression mediated by low-density lipoprotein receptor-related protein 1 in Muller cells","volume":"52","author":"Barcelona","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"13234","DOI":"10.1038\/s41598-019-49072-6","article-title":"Activated alpha2-Macroglobulin Regulates LRP1 Levels at the Plasma Membrane through the Activation of a Rab10-dependent Exocytic Pathway in Retinal Muller Glial Cells","volume":"9","author":"Jaldin-Fincati","year":"2019","journal-title":"Sci Rep"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neuropharm.2014.11.015","article-title":"Activation of Wnt\/beta-catenin signaling in Muller glia protects photoreceptors in a mouse model of inherited retinal degeneration","volume":"91","author":"Patel","year":"2015","journal-title":"Neuropharmacology"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1002\/glia.v58:7","article-title":"Involvement of gp130-associated cytokine signaling in Muller cell activation following optic nerve lesion","volume":"58","author":"Kirsch","year":"2010","journal-title":"Glia"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"E4520","DOI":"10.1073\/pnas.1303604110","article-title":"CNTF-mediated protection of photoreceptors requires initial activation of the cytokine receptor gp130 in Muller glial cells","volume":"110","author":"Rhee","year":"2013","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=2778020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:26Z","timestamp":1791927086000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2778020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,26]]},"references-count":37,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2021,10,4]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.62.13.23","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2021,10,26]]}}}