{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:38:50Z","timestamp":1760143130162,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science KAKENHI (Scientific Research (C))","award":["15K07971","18K06689"],"award-info":[{"award-number":["15K07971","18K06689"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glaucoma is one of the leading causes of acquired blindness and characterized by retinal ganglion cell (RGC) death. MicroRNAs are small noncoding RNAs that degrade their target mRNAs. Apoptosis is one of the common mechanisms leading to neuronal death in many neurodegenerative diseases, including glaucoma. In the present study, we identified microRNAs that modulate RGC death caused by the intravitreal injection of N-methyl-d-aspartic acid (NMDA). We found an upregulation of miR-29b and downregulation of miR-124 in the retina of the NMDA-injected eyes. The intravitreal injection of an miR-29b inhibitor 18 h before NMDA injection reduced RGC death and the downregulation of myeloid cell leukemia 1 (MCL-1), an anti-apoptotic factor, induced by intravitreal NMDA. The intravitreal injection of an miR-124 mimic 18 h before NMDA injection also reduced RGC death and the upregulation of B-cell\/chronic lymphocytic leukemia lymphoma 2 (bcl-2)-associated X protein (Bax) and bcl-2 interacting protein (Bim), pro-apoptotic factors, induced by intravitreal NMDA. These data suggest that expressional changes in microRNA are involved in the excitotoxicity of RGCs, and that complement and\/or inhibition of microRNA may be a potential therapeutic approach for the diseases related to the excitotoxicity of RGCs, such as glaucoma and retinal central artery occlusion.<\/jats:p>","DOI":"10.3390\/ijms25021106","type":"journal-article","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T11:37:18Z","timestamp":1705405038000},"page":"1106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Role of microRNAs Related to Apoptosis for N-Methyl-d-Aspartic Acid-Induced Neuronal Cell Death in the Murine Retina"],"prefix":"10.3390","volume":"25","author":[{"given":"Kohei","family":"Sone","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-Chome, Minato-ku, Tokyo 108-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7188-9984","authenticated-orcid":false,"given":"Asami","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-Chome, Minato-ku, Tokyo 108-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1326-6580","authenticated-orcid":false,"given":"Kenji","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-Chome, Minato-ku, Tokyo 108-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7579-5870","authenticated-orcid":false,"given":"Tsutomu","family":"Nakahara","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-Chome, Minato-ku, Tokyo 108-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1016\/S0140-6736(23)01289-8","article-title":"Glaucoma: Now and beyond","volume":"402","author":"Jayaram","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1523\/JNEUROSCI.07-02-00369.1987","article-title":"Ionic dependence of glutamate neurotoxicity in cortical cell culture","volume":"7","author":"Choi","year":"1987","journal-title":"J. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/0166-2236(88)90200-7","article-title":"Calcium-mediated neurotoxicity: Relationship to specific channel types and role in ischemic damage","volume":"11","author":"Choi","year":"1988","journal-title":"Trends Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.ohc.2005.04.002","article-title":"Retinal ganglion cell death in glaucoma: Mechanisms and neuroprotective strategies","volume":"18","author":"Kuehn","year":"2005","journal-title":"Ophthalmol. Clin. N. Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nrg1379","article-title":"MicroRNAs: Small RNAs with a big role in gene regulation","volume":"5","author":"He","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41580-018-0045-7","article-title":"Regulation of microRNA function in animals","volume":"20","author":"Gebert","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.4161\/cc.9.9.11296","article-title":"MicroRNAs in neurodegenerative disorders","volume":"9","author":"Junn","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.pharmthera.2011.10.002","article-title":"MicroRNAs in neurodegenerative diseases and their therapeutic potential","volume":"133","author":"Junn","year":"2012","journal-title":"Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrd.2016.246","article-title":"MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases","volume":"16","author":"Rupaimoole","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7971","DOI":"10.1167\/iovs.15-18088","article-title":"MicroRNA Expression in the Glaucomatous Retina","volume":"56","author":"Jayaram","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6133","DOI":"10.1038\/sj.onc.1210436","article-title":"mir-29 regulates Mcl-1 protein expression and apoptosis","volume":"26","author":"Mott","year":"2007","journal-title":"Oncogene"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"35423","DOI":"10.1038\/srep35423","article-title":"The microRNA expression profile of mouse M\u00fcller glia in vivo and in vitro","volume":"6","author":"Wohl","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.brainres.2006.11.035","article-title":"RT-PCR-based analysis of microRNA (miR-1 and -124) expression in mouse CNS","volume":"1131","author":"Mishima","year":"2007","journal-title":"Brain Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1038\/nn.2897","article-title":"miR-124a is required for hippocampal axogenesis and retinal cone survival through Lhx2 suppression","volume":"14","author":"Sanuki","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_15","first-page":"14465","article-title":"MiR-124 effect in neurons apoptosis in newborn rat with thyroid hypofunction","volume":"8","author":"Shao","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/bpa.12267","article-title":"MiR-124 Regulates Apoptosis and Autophagy Process in MPTP Model of Parkinson\u2019s Disease by Targeting to Bim","volume":"26","author":"Wang","year":"2016","journal-title":"Brain Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e15539","DOI":"10.1016\/j.heliyon.2023.e15539","article-title":"microRNA-96 targets the INS\/AKT\/GLUT4 signaling axis: Association with and effect on diabetic retinopathy","volume":"9","author":"Zolfaghari","year":"2023","journal-title":"Heliyon"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"B\u0142aszkiewicz, M., Walulik, A., Florek, K., G\u00f3recki, I., S\u0142awatyniec, O., and Gomu\u0142ka, K. (2023). Advances and Perspectives in Relation to the Molecular Basis of Diabetic Retinopathy-A Review. Biomedicines, 11.","DOI":"10.3390\/biomedicines11112951"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e23002","DOI":"10.1016\/j.heliyon.2023.e23002","article-title":"Identification of a novel ferroptosis-related gene signature associated with retinal degeneration induced by light damage in mice","volume":"9","author":"Lei","year":"2023","journal-title":"Heliyon"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106805","DOI":"10.1016\/j.prostaglandins.2023.106805","article-title":"12-HETE activates M\u00fcller glial cells: The potential role of GPR31 and miR-29","volume":"171","author":"Moustafa","year":"2023","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Jiang, W., He, S., Liu, L., Meng, X., Lu, J., Li, J., Chen, T., Xu, Y., Xiao, Q., and Qi, L. (2023). New insights on the role of microRNAs in retinal M\u00fcller glial cell function. Br. J. Ophthalmol., published online first.","DOI":"10.1136\/bjo-2023-324132"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"107237","DOI":"10.1016\/j.isci.2023.107237","article-title":"Light-responsive microRNA molecules in human retinal organoids are differentially regulated by distinct wavelengths of light","volume":"26","author":"Celiker","year":"2023","journal-title":"iScience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15812","DOI":"10.1038\/srep15812","article-title":"\u03b1-Melanocyte-stimulating hormone prevents glutamate excitotoxicity in developing chicken retina via MC4R-mediated down-regulation of microRNA-194","volume":"5","author":"Zhang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1167\/iovs.02-0187","article-title":"Divergent NMDA signals leading to proapoptotic and antiapoptotic pathways in the rat retina","volume":"44","author":"Manabe","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3544","DOI":"10.1167\/iovs.09-5049","article-title":"Neuroprotective effects of C-type natriuretic peptide on rat retinal ganglion cells","volume":"51","author":"Ma","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_26","first-page":"12618","article-title":"High-mobility group box-1 impedes skeletal muscle regeneration via downregulation of Pax-7 synthesis by increasing miR-342-5p expression","volume":"15","author":"Ho","year":"2023","journal-title":"Aging"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ma, H., Wang, L., Sun, H., Yu, Q., Yang, T., Wang, Y., Niu, B., Jia, Y., Liu, Y., and Liang, Z. (2023). MIR-107\/HMGB1\/FGF-2 axis responds to excessive mechanical stretch to promote rapid repair of vascular endothelial cells. Arch. Biochem. Biophys., 744.","DOI":"10.1016\/j.abb.2023.109686"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.exer.2015.06.003","article-title":"High-mobility group Box-1 is involved in NMDA-induced retinal injury the in rat retina","volume":"137","author":"Sakamoto","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_29","first-page":"33","article-title":"Involvement of microRNA-181a and Bim in a rat model of retinal ischemia-reperfusion injury","volume":"9","author":"He","year":"2016","journal-title":"Int. J. Ophthalmol."},{"key":"ref_30","unstructured":"Sone, K., Mori, A., Sakamoto, K., and Nakahara, T. Unpublished work."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"D149","DOI":"10.1093\/nar\/gkm995","article-title":"The microRNA.org resource: Targets and expression","volume":"36","author":"Betel","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1111\/j.1365-2141.2004.04949.x","article-title":"Characterisation of Mcl-1 cleavage during apoptosis of haematopoietic cells","volume":"125","author":"Clohessy","year":"2004","journal-title":"Br. J. Haematol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6068","DOI":"10.1523\/JNEUROSCI.4940-07.2008","article-title":"Mcl-1 is a key regulator of apoptosis during CNS development and after DNA damage","volume":"28","author":"Arbour","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1016\/j.febslet.2010.05.061","article-title":"Mcl-1; the molecular regulation of protein function","volume":"584","author":"Thomas","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e00032","DOI":"10.1042\/AN20100003","article-title":"A single nucleotide polymorphism in the Bax gene promoter affects transcription and influences retinal ganglion cell death","volume":"2","author":"Semaan","year":"2010","journal-title":"ASN Neuro"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1083\/jcb.200909166","article-title":"AMP kinase-mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis","volume":"189","author":"Concannon","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.exer.2008.12.011","article-title":"Histological protection by cilnidipine, a dual L\/N-type Ca2+ channel blocker, against neurotoxicity induced by ischemia-reperfusion in rat retina","volume":"88","author":"Sakamoto","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ejphar.2014.03.035","article-title":"Activation of the TRPV1 channel attenuates N-methyl-D-aspartic acid-induced neuronal injury in the rat retina","volume":"733","author":"Sakamoto","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1248\/bpb.b17-01032","article-title":"GYY4137, an Extended-Release Hydrogen Sulfide Donor, Reduces NMDA-Induced Neuronal Injury in the Murine Retina","volume":"41","author":"Sone","year":"2018","journal-title":"Biol. Pharm. Bull."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/1106\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:48:08Z","timestamp":1760104088000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/1106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,16]]},"references-count":40,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25021106"],"URL":"https:\/\/doi.org\/10.3390\/ijms25021106","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,1,16]]}}}