{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T17:24:51Z","timestamp":1775841891625,"version":"3.50.1"},"reference-count":62,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870656"],"award-info":[{"award-number":["81870656"]}],"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":["2017A030313610"],"award-info":[{"award-number":["2017A030313610"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Accumulating evidence suggests that the complement C3\/C3a receptor (C3aR) pathway plays a pivotal role in the pathogenesis of neurodegenerative and autoimmune disorders, particularly neuromyelitis optica spectrum disorders (NMOSDs). Despite this, the specific pathogenic effect and mechanism of C3\/C3aR pathway in NMOSD remains elusive. In this study, we demonstrated for the first time that the expression of C3aR and its upstream ligand C3 is significantly upregulated in the optic nerve of a rat model of NMOSD\u2010related optic neuritis (NMOSD\u2010ON). Our findings reveal that this upregulation leads to blood\u2013brain barrier (BBB) disruption, demyelination and neuronal damage. Through the use of a novel C3aR inhibitor, JR14a, we demonstrate its effectiveness in reducing C3aR expression and mitigating pathological damage in the optic nerve. Furthermore, our transcriptome sequencing analysis of NMOSD optic nerve tissues reveals extensive enrichment of inflammation\u2010 and immune response\u2013related pathways, with particular emphasis on the complement and coagulation cascades pathway. This study not only elucidated the crucial role of the C3\u2010C3aR pathway in NMOSD\u2010ON pathogenesis but also provided a new promising therapeutic target for NMOSD through C3aR pathway inhibition.<\/jats:p>","DOI":"10.1111\/ejn.70103","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T09:10:02Z","timestamp":1745313002000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of C3\/C3aR Pathway Alleviates Visual and Optic Nerve Impairments in a Rat Model of Neuromyelitis Optica Spectrum Disorder"],"prefix":"10.1111","volume":"61","author":[{"given":"Siqi","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat\u2010sen University Guangdong Provincial Key Laboratory of Ophthalmology Visual Science  Guangzhou Guangdong Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yurong","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat\u2010sen University Guangdong Provincial Key Laboratory of Ophthalmology Visual Science  Guangzhou Guangdong Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiqun","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat\u2010sen University Guangdong Provincial Key Laboratory of Ophthalmology Visual Science  Guangzhou Guangdong Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqiang","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat\u2010sen University Guangdong Provincial Key Laboratory of Ophthalmology Visual Science  Guangzhou Guangdong Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoning","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat\u2010sen University Guangdong Provincial Key Laboratory of Ophthalmology Visual Science  Guangzhou Guangdong Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyan","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat\u2010sen University Guangdong Provincial Key Laboratory of Ophthalmology Visual Science  Guangzhou Guangdong Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Neurology The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou Guangdong Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangdong\u2010Hong Kong\u2010Macau Institute of CNS Regeneration, Key Laboratory of CNS Regeneration (Ministry of Education) Jinan University  Guangzhou Guangdong Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changyong","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou Guangdong Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5643-4711","authenticated-orcid":false,"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat\u2010sen University Guangdong Provincial Key Laboratory of Ophthalmology Visual Science  Guangzhou Guangdong Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000360619"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1204-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-11-16"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2021.1884223"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI144348"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI134816"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.3929"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.227298"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-0400-0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1333-z"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2009.139"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2021101384"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.12.015"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2017.11.007"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2011.00512.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2011.04.009"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004611"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0214-9"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-020-00230-3"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000269"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2013.03.001"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2021.577506"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.853891"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.10.031"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24271"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458520981736"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2024.110012"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0577-8"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2017.01.024"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2013.12.010"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02623-7"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2021.102741"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2014.07.001"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S322789"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3109\/13550289909021285"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI140966"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00927"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp309"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aai9111"},{"key":"e_1_2_9_42_1","doi-asserted-by":"crossref","DOI":"10.1002\/brb3.584","article-title":"Elevated Cerebrospinal Fluid Uric Acid During Relapse of Neuromyelitis Optica Spectrum Disorders","volume":"7","author":"Shu Y.","year":"2017","journal-title":"Brain and Behavior: A Cognitive Neuroscience Perspective"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2018"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000001076"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2024.110986"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108927"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2013-305907"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458516672015"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458510379247"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13415"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2484"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23955"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001729"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI141694"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.07.017"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-017-0417-9"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-7434"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13147"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458519887905"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2014.02.011"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.705536"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05807-y"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2018.06.011"}],"container-title":["European Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejn.70103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T07:27:56Z","timestamp":1762932476000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejn.70103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":62,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/ejn.70103"],"URL":"https:\/\/doi.org\/10.1111\/ejn.70103","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/EJN.70103\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.70103\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.70103\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.70103\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.70103\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.70103\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.70103\/v2\/response1","asserted-by":"object"}]},"ISSN":["0953-816X","1460-9568"],"issn-type":[{"value":"0953-816X","type":"print"},{"value":"1460-9568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2024-12-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70103"}}