{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:22:13Z","timestamp":1791861733114,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000615","name":"Fight for Sight UK","doi-asserted-by":"publisher","award":["24WGIGA"],"award-info":[{"award-number":["24WGIGA"]}],"id":[{"id":"10.13039\/501100000615","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The purpose of this study was to characterize the miRNA profile of purified retinal ganglion cells (RGC) from healthy and diseased rat retina. Diseased retina includes those after a traumatic optic nerve crush (ONC), and after ocular hypertension\/glaucoma. Rats were separated into four groups: healthy\/intact, 7 days after laser-induced ocular hypertension, 2 days after traumatic ONC, and 7 days after ONC. RGC were purified from rat retina using microbeads conjugated to CD90.1\/Thy1. RNA were sequenced using Next Generation Sequencing. Over 100 miRNA were identified that were significantly different in diseased retina compared to healthy retina. Considerable differences were seen in the miRNA expression of RGC 7 days after ONC, whereas after 2 days, few changes were seen. The miRNA profiles of RGC 7 days after ONC and 7 days after ocular hypertension were similar, but discrete miRNA differences were still seen. Candidate mRNA showing different levels of expression after retinal injury were manipulated in RGC cultures using mimics\/AntagomiRs. Of the five candidate miRNA identified and subsequently tested for therapeutic efficacy, miR-194 inhibitor and miR-664-2 inhibitor elicited significant RGC neuroprotection, whereas miR-181a mimic and miR-181d-5p mimic elicited significant RGC neuritogenesis.<\/jats:p>","DOI":"10.3390\/cells10071564","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T13:02:10Z","timestamp":1624366930000},"page":"1564","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["miRNA Changes in Retinal Ganglion Cells after Optic Nerve Crush and Glaucomatous Damage"],"prefix":"10.3390","volume":"10","author":[{"given":"Ben","family":"Mead","sequence":"first","affiliation":[{"name":"School of Optometry and Vision Sciences, Cardiff University, Cardiff CF24 4HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Kerr","sequence":"additional","affiliation":[{"name":"Section of Retinal Ganglion Cell Biology, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Nakaya","sequence":"additional","affiliation":[{"name":"Section of Retinal Ganglion Cell Biology, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav I.","family":"Tomarev","sequence":"additional","affiliation":[{"name":"Section of Retinal Ganglion Cell Biology, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,22]]},"reference":[{"key":"ref_1","first-page":"147","article-title":"Regeneration of axons in the visual system","volume":"26","author":"Berry","year":"2008","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4368","DOI":"10.1523\/JNEUROSCI.14-07-04368.1994","article-title":"Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats","volume":"14","author":"Berkelaar","year":"1994","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global prevalence of glaucoma and projections of glaucoma burden through 2040","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_5","doi-asserted-by":"crossref","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":"ref_6","doi-asserted-by":"crossref","unstructured":"Calkins, D.J. (2021). Adaptive responses to neurodegenerative stress in glaucoma. Prog. Retin. Eye Res., 100953.","DOI":"10.1016\/j.preteyeres.2021.100953"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"M\u00e9lik Parsadaniantz, S., R\u00e9aux-le Goazigo, A., Sapienza, A., Habas, C., and Baudouin, C. (2020). Glaucoma: A degenerative optic neuropathy related to neuroinflammation?. Cells, 9.","DOI":"10.3390\/cells9030535"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1007\/s12035-019-01783-7","article-title":"Bax-depleted retinal ganglion cells survive and become quiescent following optic nerve damage","volume":"57","author":"Donahue","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Libby, R.T., Li, Y., Savinova, O.V., Barter, J., Smith, R.S., Nickells, R.W., and John, S.W.M. (2005). Susceptibility to neurodegeneration in a glaucoma is modified by bax gene dosage. PLoS Genet., 1.","DOI":"10.1371\/journal.pgen.0010004"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.scr.2015.02.003","article-title":"Stem cell treatment of degenerative eye disease","volume":"14","author":"Mead","year":"2015","journal-title":"Stem Cell Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"100849","DOI":"10.1016\/j.preteyeres.2020.100849","article-title":"Extracellular vesicle therapy for retinal diseases","volume":"79","author":"Mead","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1038\/s41598-019-39141-1","article-title":"Transcriptomic profiles of retinal ganglion cells are defined by the magnitude of intraocular pressure elevation in adult mice","volume":"9","author":"Park","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1038\/s41467-018-05134-3","article-title":"Single cell transcriptome profiling of retinal ganglion cells identifies cellular subtypes","volume":"9","author":"Rheaume","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1167\/iovs.17-23599","article-title":"Microrna profiling in glaucoma eyes with varying degrees of optic neuropathy by using next-generation sequencing","volume":"59","author":"Liu","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zuzic, M., Rojo Arias, J.E., Wohl, S.G., and Busskamp, V. (2019). Retinal mirna functions in health and disease. Genes, 10.","DOI":"10.3390\/genes10050377"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Brennecke, J., Stark, A., Russell, R.B., and Cohen, S.M. (2005). Principles of microrna\u2013target recognition. PLoS Biol., 3.","DOI":"10.1371\/journal.pbio.0030085"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.15252\/embj.201488142","article-title":"Mirnas at the interface of cellular stress and disease","volume":"33","author":"Emde","year":"2014","journal-title":"EMBO J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.molcel.2010.09.027","article-title":"Microrna functions in stress responses","volume":"40","author":"Leung","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/s41576-020-00309-5","article-title":"The roles of micrornas in mouse development","volume":"22","author":"DeVeale","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"ref_21","first-page":"402","article-title":"Translimbal laser photocoagulation to the trabecular meshwork as a model of glaucoma in rats","volume":"43","author":"Quigley","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1167\/iovs.17-22855","article-title":"Mesenchymal stem cell\u2013derived small extracellular vesicles promote neuroprotection in rodent models of glaucoma","volume":"59","author":"Mead","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e45881","DOI":"10.7554\/eLife.45881","article-title":"Silicone oil-induced ocular hypertension and glaucomatous neurodegeneration in mouse","volume":"8","author":"Zhang","year":"2019","journal-title":"eLife"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/BF02284793","article-title":"Peripheral nerve explants grafted into the vitreous body of the eye promote the regeneration of retinal ganglion cell axons severed in the optic nerve","volume":"25","author":"Berry","year":"1996","journal-title":"J. Neurocytol."},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.bbrc.2011.05.004","article-title":"Mirna profiling of bilateral rat hippocampal ca3 by deep sequencing","volume":"409","author":"Shinohara","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yao, M.-j., Chen, G., Zhao, P.-p., Lu, M.-h., Jian, J., Liu, M.-f., and Yuan, X.-b. (2012). Transcriptome analysis of micrornas in developing cerebral cortex of rat. BMC Genom., 13.","DOI":"10.1186\/1471-2164-13-232"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8936","DOI":"10.1523\/JNEUROSCI.18-21-08936.1998","article-title":"The major cell populations of the mouse retina","volume":"18","author":"Jeon","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Carrella, S., Barbato, S., D\u2019Agostino, Y., Salierno, F.G., Manfredi, A., Banfi, S., and Conte, I. (2015). Tgf-\u03b2 controls mir-181\/erk regulatory network during retinal axon specification and growth. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144129"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.mcn.2009.01.004","article-title":"Optimisation of sirna-mediated rhoa silencing in neuronal cultures","volume":"40","author":"Suggate","year":"2009","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Indrieri, A., Carrella, S., Carotenuto, P., Banfi, S., and Franco, B. (2020). The pervasive role of the mir-181 family in development, neurodegeneration, and cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062092"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.expneurol.2014.11.007","article-title":"Post-stroke treatment with mir-181 antagomir reduces injury and improves long-term behavioral recovery in mice after focal cerebral ischemia","volume":"264","author":"Xu","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e8734","DOI":"10.15252\/emmm.201708734","article-title":"Mir-181a\/b downregulation exerts a protective action on mitochondrial disease models","volume":"11","author":"Indrieri","year":"2019","journal-title":"EMBO Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"14044","DOI":"10.1038\/s41598-018-32426-x","article-title":"Microrna-194-5p levels decrease during deep hypothermic circulatory arrest","volume":"8","author":"Wang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"71292","DOI":"10.18632\/oncotarget.19772","article-title":"Mir-708-5p: A microrna with emerging roles in cancer","volume":"8","author":"Monteleone","year":"2017","journal-title":"Oncotarget"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.nbd.2015.10.002","article-title":"Prospects for mtor-mediated functional repair after central nervous system trauma","volume":"85","author":"Berry","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/gtc.12559","article-title":"Microrna-664a-5p promotes neuronal differentiation of sh-sy5y cells","volume":"23","author":"Watanabe","year":"2018","journal-title":"Genes Cells"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"19177","DOI":"10.1074\/jbc.RA118.003198","article-title":"Microrna-664-5p promotes myoblast proliferation and inhibits myoblast differentiation by targeting serum response factor and wnt1","volume":"293","author":"Cai","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"C839","DOI":"10.1152\/ajpcell.00324.2017","article-title":"Downregulation of microrna-149 in retinal ganglion cells suppresses apoptosis through activation of the pi3k\/akt signaling pathway in mouse with glaucoma","volume":"15","author":"Nie","year":"2018","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biopha.2018.01.044","article-title":"Mir-93-5p targeting pten regulates the nmda-induced autophagy of retinal ganglion cells via akt\/mtor pathway in glaucoma","volume":"100","author":"Li","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.neulet.2009.10.077","article-title":"Cyan fluorescent protein (cfp) expressing cells in the retina of thy1-cfp transgenic mice before and after optic nerve injury","volume":"468","author":"Wang","year":"2010","journal-title":"Neurosci. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1002\/cne.23521","article-title":"The rna binding protein rbpms is a selective marker of ganglion cells in the mammalian retina","volume":"522","author":"Rodriguez","year":"2014","journal-title":"J. Comp. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"108071","DOI":"10.1016\/j.exer.2020.108071","article-title":"Viral delivery of multiple mirnas promotes retinal ganglion cell survival and functional preservation after optic nerve crush injury","volume":"197","author":"Mead","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"586130","DOI":"10.3389\/fbioe.2020.586130","article-title":"Recent advancements in the loading and modification of therapeutic exosomes","volume":"8","author":"Xu","year":"2020","journal-title":"Front. Bioeng. Biotechnol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/7\/1564\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:20:39Z","timestamp":1760163639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/7\/1564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,22]]},"references-count":44,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["cells10071564"],"URL":"https:\/\/doi.org\/10.3390\/cells10071564","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,22]]}}}