{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T16:27:35Z","timestamp":1784910455900,"version":"3.55.0"},"reference-count":52,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T00:00:00Z","timestamp":1655164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81900858"],"award-info":[{"award-number":["81900858"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2018A030310185"],"award-info":[{"award-number":["2018A030310185"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2020YFA0112701"],"award-info":[{"award-number":["2020YFA0112701"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["81900858"],"award-info":[{"award-number":["81900858"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2018A030310185"],"award-info":[{"award-number":["2018A030310185"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2020YFA0112701"],"award-info":[{"award-number":["2020YFA0112701"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Research and Development Project of China","award":["81900858"],"award-info":[{"award-number":["81900858"]}]},{"name":"National Key Research and Development Project of China","award":["2018A030310185"],"award-info":[{"award-number":["2018A030310185"]}]},{"name":"National Key Research and Development Project of China","award":["2020YFA0112701"],"award-info":[{"award-number":["2020YFA0112701"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Purpose: Previous studies have found the neurodegeneration and atrophy of glaucomatous lateral geniculate nucleus (LGN), but the mechanism is still unknown. Circular RNA (circRNA) plays some important roles in physiological and pathological progression of the disease. In this study, we focused on the differentially expressed circRNAs and the mechanism for circXPO5 in LGN degeneration in a macaque glaucoma model. Methods: Using RNA-seq, we analyzed the differentially expressed circRNAs in a macaque glaucoma model. An RT-QPCR was used to check the expression of selected differentially expressed circRNAs, candidate miRNAs and mRNAs. A competing endogenous RNA (ceRNA) network analysis was performed to examine the mechanism of circXPO5 action. Results: circXPO5 significantly decreased in the glaucoma model and a ceRNA network analysis revealed that circXPO5 can bind to miR-330-5p, which also binds to GRIN2A (ionotropic receptor NMDA type subunit 2A). QPCR detection showed a decrease in GRIN2A and an increase in miR-330-5p. Conclusions: Our earlier studies revealed that the GRIN2A gene regulates the calcium signal pathway. Decreasing of GRIN2A related with neuron apoptosis and neurodegeneration. These findings indicate that the reduction in circXPO5 may have a protective effect on neuronal apoptosis in the visual central system of glaucoma.<\/jats:p>","DOI":"10.3390\/brainsci12060780","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T23:50:14Z","timestamp":1655250614000},"page":"780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["CircXPO5 Plays a Neuroprotective Function in the Lateral Geniculate Nucleus of Glaucoma by Regulating GRIN2A"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1442-3015","authenticated-orcid":false,"given":"Zhichao","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Glaucoma and Neuro-Ophthalmology, Shenzhen Eye Hospital, Shenzhen Eye Institute, Jinan University, School of Optometry, Shenzhen University, Shenzhen 518040, China"},{"name":"Department of Ophthalmology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingying","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Glaucoma and Neuro-Ophthalmology, Shenzhen Eye Hospital, Shenzhen Eye Institute, Jinan University, School of Optometry, Shenzhen University, Shenzhen 518040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5276-5852","authenticated-orcid":false,"given":"Yu","family":"Jia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caibin","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehong","family":"Zhuo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1016\/S0140-6736(17)31469-1","article-title":"Glaucoma","volume":"390","author":"Jonas","year":"2017","journal-title":"Lancet"},{"key":"ref_2","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: A systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1001\/jama.2014.3192","article-title":"The pathophysiology and treatment of glaucoma: A review","volume":"311","author":"Weinreb","year":"2014","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"119","DOI":"10.15283\/ijsc17029","article-title":"Glaucoma, Stem Cells, and Gene Therapy: Where Are We Now?","volume":"10","author":"Daliri","year":"2017","journal-title":"Int. J. Stem Cells"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/s41433-018-0050-2","article-title":"Neuroprotective agents in the management of glaucoma","volume":"32","author":"Nucci","year":"2018","journal-title":"Eye"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5434","DOI":"10.1167\/iovs.17-22312","article-title":"Elevated Intraocular Pressure Induces Amyloid-beta Deposition and Tauopathy in the Lateral Geniculate Nucleus in a Monkey Model of Glaucoma","volume":"58","author":"Yan","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.survophthal.2017.09.010","article-title":"Glaucoma and the brain: Trans-synaptic degeneration, structural change, and implications for neuroprotection","volume":"63","author":"Lawlor","year":"2018","journal-title":"Surv. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1111\/j.1460-9568.2010.07578.x","article-title":"Involvement of endoplasmic reticulum stress on neuronal cell death in the lateral geniculate nucleus in the monkey glaucoma model","volume":"33","author":"Ito","year":"2011","journal-title":"Eur. J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0301-0082(99)00007-6","article-title":"Subunit- and site-specific pharmacology of the NMDA receptor channel","volume":"59","author":"Yamakura","year":"1999","journal-title":"Prog. Neurobiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1056\/NEJMcibr0902052","article-title":"Memory and the NMDA receptors","volume":"361","author":"Li","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_11","first-page":"7","article-title":"The glutamate receptor ion channels","volume":"51","author":"Dingledine","year":"1999","journal-title":"Pharmacol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/jnr.24153","article-title":"Activation of caspase-6 and cleavage of caspase-6 substrates is an early event in NMDA receptor-mediated excitotoxicity","volume":"96","author":"Girling","year":"2018","journal-title":"J. Neurosci. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11295","DOI":"10.1523\/JNEUROSCI.5612-10.2011","article-title":"Arrangement of subunits in functional NMDA receptors","volume":"31","author":"Salussolia","year":"2011","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1006\/geno.1997.5132","article-title":"Localization of the human NMDAR2D receptor subunit gene (GRIN2D) to 19q13.1-qter, the NMDAR2A subunit gene to 16p13.2 (GRIN2A), and the NMDAR2C subunit gene (GRIN2C) to 17q24-q25 using somatic cell hybrid and radiation hybrid mapping panels","volume":"47","author":"Kalsi","year":"1998","journal-title":"Genomics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s12031-021-01893-9","article-title":"Integrated Bioinformatics Analysis to Identify Alternative Therapeutic Targets for Alzheimer\u2019s Disease: Insights from a Synaptic Machinery Perspective","volume":"72","author":"Ceylan","year":"2022","journal-title":"J. Mol. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1254\/jphs.CPJ04006X","article-title":"Mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis in Alzheimer\u2019s disease","volume":"97","author":"Takuma","year":"2005","journal-title":"J. Pharmacol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1805304","DOI":"10.1155\/2016\/1805304","article-title":"Killing Me Softly: Connotations to Unfolded Protein Response and Oxidative Stress in Alzheimer\u2019s Disease","volume":"2016","author":"Pajak","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/cr.2017.70","article-title":"Circular RNAs: Coding or noncoding?","volume":"27","author":"Schneider","year":"2017","journal-title":"Cell Res"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.pharmthera.2018.01.010","article-title":"Circular RNA and its mechanisms in disease: From the bench to the clinic","volume":"187","author":"Han","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1016\/j.ymthe.2019.07.001","article-title":"Circular RNAs: A Novel Class of Functional RNA Molecules with a Therapeutic Perspective","volume":"27","author":"Santer","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq--a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count data","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1186\/gb-2003-5-1-r1","article-title":"MicroRNA targets in Drosophila","volume":"5","author":"Enright","year":"2003","journal-title":"Genome Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1038\/ng.2007.2","article-title":"Network modeling links breast cancer susceptibility and centrosome dysfunction","volume":"39","author":"Pujana","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6217","DOI":"10.1038\/s41598-022-09572-4","article-title":"MicroRNA profiles in aqueous humor between pseudoexfoliation glaucoma and normal tension glaucoma patients in a Korean population","volume":"12","author":"Cho","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"793638","DOI":"10.3389\/fcell.2021.793638","article-title":"Network Integration Analysis and Immune Infiltration Analysis Reveal Potential Biomarkers for Primary Open-Angle Glaucoma","volume":"9","author":"Wang","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Li, H., Ye, Z., and Li, Z. (2022). Identification of the potential biological target molecules related to primary open-angle glaucoma. BMC Ophthalmol., 22.","DOI":"10.1186\/s12886-022-02368-0"},{"key":"ref_29","first-page":"273","article-title":"Mini-Review: Impaired Axonal Transport and Glaucoma","volume":"41","author":"Fahy","year":"2016","journal-title":"Curr. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.exer.2017.12.013","article-title":"Genomic loci modulating retinal ganglion cell death following elevated IOP in the mouse","volume":"169","author":"Struebing","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_31","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_32","first-page":"1226","article-title":"Research progress of stem cells on glaucomatous optic nerve injury","volume":"9","author":"Zhou","year":"2016","journal-title":"Int. J. Ophthalmol."},{"key":"ref_33","first-page":"73","article-title":"Neurodegeneration and Neuroprotection in Glaucoma","volume":"89","author":"Gauthier","year":"2016","journal-title":"Yale J. Biol. Med."},{"key":"ref_34","first-page":"1791","article-title":"Glaucoma in primates: Cytochrome oxidase reactivity in parvo- and magnocellular pathways","volume":"41","author":"Crawford","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","first-page":"2217","article-title":"Astrocyte and microglial activation in the lateral geniculate nucleus and visual cortex of glaucomatous and optic nerve transected primates","volume":"15","author":"Lam","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Shimazawa, M., Ito, Y., Inokuchi, Y., Yamanaka, H., Nakanishi, T., Hayashi, T., Ji, B., Higuchi, M., Suhara, T., and Imamura, K. (2012). An alteration in the lateral geniculate nucleus of experimental glaucoma monkeys: In vivo positron emission tomography imaging of glial activation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030526"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"591.e9","DOI":"10.1016\/j.crad.2018.01.010","article-title":"Microstructural visual pathway abnormalities in patients with primary glaucoma: 3 T diffusion kurtosis imaging study","volume":"73","author":"Xu","year":"2018","journal-title":"Clin. Radiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1111\/opo.12293","article-title":"Using magnetic resonance imaging to assess visual deficits: A review","volume":"36","author":"Brown","year":"2016","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.exer.2004.08.016","article-title":"Oxidative injury by peroxynitrite in neural and vascular tissue of the lateral geniculate nucleus in experimental glaucoma","volume":"80","author":"Luthra","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3389\/fncel.2017.00053","article-title":"Synaptic Dysfunction in Alzheimer\u2019s Disease and Glaucoma: From Common Degenerative Mechanisms Toward Neuroprotection","volume":"11","author":"Criscuolo","year":"2017","journal-title":"Front. Cell Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0002-9394(01)01196-5","article-title":"Association of glaucoma with neurodegenerative diseases with apoptotic cell death: Alzheimer\u2019s disease and Parkinson\u2019s disease","volume":"133","author":"Bayer","year":"2002","journal-title":"Am. J. Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"214","DOI":"10.3389\/fnagi.2017.00214","article-title":"The Role of Microglia in Retinal Neurodegeneration: Alzheimer\u2019s Disease, Parkinson, and Glaucoma","volume":"9","author":"Ramirez","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_43","first-page":"2647","article-title":"Induction of amyloid-beta(1-42) in the retina and optic nerve head of chronic ocular hypertensive monkeys","volume":"18","author":"Ito","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_44","first-page":"2698","article-title":"Beta Amyloid and Retinal Ganglion Cell Apoptosis: Implications and Applications to Glaucoma","volume":"47","author":"Cordeiro","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5785","DOI":"10.1523\/JNEUROSCI.3986-15.2016","article-title":"Tau Accumulation, Altered Phosphorylation, and Missorting Promote Neurodegeneration in Glaucoma","volume":"36","author":"Chiasseu","year":"2016","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"326","DOI":"10.3389\/fnins.2019.00326","article-title":"Elevated Plasma Levels of Drebrin in Glaucoma Patients With Neurodegeneration","volume":"13","author":"Gan","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3109\/00207454.2012.746974","article-title":"Signaling pathways involved in endoplasmic reticulum stress-induced neuronal apoptosis","volume":"123","author":"Liu","year":"2013","journal-title":"Int. J. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/47513","article-title":"Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta","volume":"403","author":"Nakagawa","year":"2000","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1007\/s12035-012-8301-x","article-title":"Endoplasmic reticulum enrollment in Alzheimer\u2019s disease","volume":"46","author":"Viana","year":"2012","journal-title":"Mol. Neurobiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s12031-015-0498-5","article-title":"Caspase-8 Mediates Amyloid-beta-induced Apoptosis in Differentiated PC12 Cells","volume":"56","author":"Qian","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s12011-019-01903-3","article-title":"Endoplasmic Reticulum Stress Induced by Toxic Elements-a Review of Recent Developments","volume":"196","author":"Rana","year":"2020","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3389\/fnmol.2017.00027","article-title":"Rpph1 Upregulates CDC42 Expression and Promotes Hippocampal Neuron Dendritic Spine Formation by Competing with miR-330-5p","volume":"10","author":"Cai","year":"2017","journal-title":"Front. Mol. Neurosci."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/12\/6\/780\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:31:27Z","timestamp":1760139087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/12\/6\/780"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,14]]},"references-count":52,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["brainsci12060780"],"URL":"https:\/\/doi.org\/10.3390\/brainsci12060780","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,14]]}}}