{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:26:24Z","timestamp":1792106784132,"version":"4.4.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["02132246"],"award-info":[{"award-number":["02132246"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Retinitis pigmentosa (RP) is a group of inherited eye disorders with progressive degeneration of photoreceptors in the retina, ultimately leading to partial or complete blindness. The mechanisms underlying photoreceptor degeneration are not yet completely understood. Neuroinflammation is reported to play a pathological role in RP. However, the mechanisms that trigger neuroinflammation remain largely unknown. To address this question, we investigated the role of cyclooxygenase-1 (COX-1), a key enzyme in the conversion of arachidonic acid to proinflammatory prostaglandins, in the rd10 mouse model of RP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We backcrossed COX-1 knockout mice (COX-1<jats:sup>\u2212\/\u2212<\/jats:sup>) onto the rd10 mouse model of RP and investigated the impact of COX-1 deletion on neuroinflammation in the resulting COX-1<jats:sup>\u2212\/\u2212<\/jats:sup>\/rd10 mouse line, using a combination of immunocytochemistry, flow cytometry, qPCR, ELISA, and a series of simple visual tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that genetic ablation or pharmacological inhibition of COX-1 alleviated neuroinflammation and subsequently preserved retinal photoreceptor and function and visual performance in rd10 mice. Moreover, we observed that the pharmacological inhibition of the prostaglandin E2 (PGE2) EP2 receptors largely replicated the beneficial effects of COX-1 deletion, suggesting that EP2 receptor was a critical downstream effector of COX-1-mediated neurotoxicity in rd10 mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that the COX-1\/PGE2\/EP2 signaling pathway was partly responsible for significantly increased neuroinflammation and disease progression in rd10 mice, and that EP2 receptor could be targeted therapeutically to block the pathological activity of COX-1 without inducing any potential side effects in treating RP patients.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12974-020-01993-0","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T18:05:27Z","timestamp":1602785127000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Cyclooxygenase-1 mediates neuroinflammation and neurotoxicity in a mouse model of retinitis pigmentosa"],"prefix":"10.1186","volume":"17","author":[{"given":"Wei","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyin","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1309-3480","authenticated-orcid":false,"given":"Bin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"issue":"9549","key":"1993_CR1","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1016\/S0140-6736(06)69740-7","volume":"368","author":"DT Hartong","year":"2006","unstructured":"Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006;368(9549):1795\u2013809.","journal-title":"Lancet."},{"key":"1993_CR2","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/nrg2717","volume":"11","author":"AF Wright","year":"2010","unstructured":"Wright AF, Chakarova CF, Abd El-Aziz MM, Bhattacharya SS. Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait. Nat Rev Genet. 2010;11:273\u201384.","journal-title":"Nat Rev Genet."},{"issue":"2","key":"1993_CR3","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1111\/cge.12203","volume":"84","author":"SP Daiger","year":"2013","unstructured":"Daiger SP, Sullivan LS, Bowne SJ. Genes and mutations causing retinitis pigmentosa. Clin Genet. 2013;84(2):132\u201341.","journal-title":"Clin Genet."},{"key":"1993_CR4","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/S0014-4835(02)00332-9","volume":"76","author":"N Gupta","year":"2003","unstructured":"Gupta N, Brown KE, Milam AH. Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration. Exp Eye Res. 2003;76:463\u201371.","journal-title":"Exp Eye Res."},{"issue":"6","key":"1993_CR5","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1189\/jlb.0207114","volume":"81","author":"T Langmann","year":"2007","unstructured":"Langmann T. Microglia activation in retinal degeneration. Journal of leukocyte biology. 2007;81(6):1345\u201351.","journal-title":"Journal of leukocyte biology."},{"issue":"24","key":"1993_CR6","doi-asserted-by":"publisher","first-page":"8139","DOI":"10.1523\/JNEUROSCI.5200-13.2014","volume":"34","author":"B Peng","year":"2014","unstructured":"Peng B, Xiao J, Wang K, So KF, Tipoe GL, Lin B. Suppression of microglial activation is neuroprotective in a mouse model of human retinitis pigmentosa. J Neurosci. 2014;34(24):8139\u201350.","journal-title":"J Neurosci."},{"issue":"1","key":"1993_CR7","doi-asserted-by":"publisher","first-page":"e5","DOI":"10.1016\/j.ophtha.2012.07.008","volume":"120","author":"N Yoshida","year":"2013","unstructured":"Yoshida N, Ikeda Y, Notomi S, Ishikawa K, Murakami Y, Hisatomi T, et al. Laboratory evidence of sustained chronic inflammatory reaction in retinitis pigmentosa. Ophthalmology. 2013;120(1):e5\u201312.","journal-title":"Ophthalmology."},{"issue":"9","key":"1993_CR8","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1002\/glia.23016","volume":"64","author":"MK Zabel","year":"2016","unstructured":"Zabel MK, Zhao L, Zhang Y, Gonzalez SR, Ma W, Wang X, et al. Microglial phagocytosis and activation underlying photoreceptor degeneration is regulated by CX3CL1-CX3CR1 signaling in a mouse model of retinitis pigmentosa. Glia. 2016;64(9):1479\u201391.","journal-title":"Glia."},{"issue":"9","key":"1993_CR9","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.15252\/emmm.201505298","volume":"7","author":"L Zhao","year":"2015","unstructured":"Zhao L, Zabel MK, Wang X, Ma W, Shah P, Fariss RN, et al. Microglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration. EMBO molecular medicine. 2015;7(9):1179\u201397.","journal-title":"EMBO molecular medicine."},{"issue":"9","key":"1993_CR10","doi-asserted-by":"publisher","first-page":"3591","DOI":"10.1073\/pnas.1218498110","volume":"110","author":"J Jiang","year":"2013","unstructured":"Jiang J, Quan Y, Ganesh T, Pouliot WA, Dudek FE, Dingledine R. Inhibition of the prostaglandin receptor EP2 following status epilepticus reduces delayed mortality and brain inflammation. Proc Natl Acad Sci U S A. 2013;110(9):3591\u20136.","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"40","key":"1993_CR11","doi-asserted-by":"publisher","first-page":"16016","DOI":"10.1523\/JNEUROSCI.2203-13.2013","volume":"33","author":"JU Johansson","year":"2013","unstructured":"Johansson JU, Pradhan S, Lokteva LA, Woodling NS, Ko N, Brown HD, et al. Suppression of inflammation with conditional deletion of the prostaglandin E2 EP2 receptor in macrophages and brain microglia. J Neurosci. 2013;33(40):16016\u201332.","journal-title":"J Neurosci."},{"issue":"20","key":"1993_CR12","doi-asserted-by":"publisher","first-page":"10019","DOI":"10.1073\/pnas.1818544116","volume":"116","author":"Q Liu","year":"2019","unstructured":"Liu Q, Liang X, Wang Q, Wilson EN, Lam R, Wang J, et al. PGE2 signaling via the neuronal EP2 receptor increases injury in a model of cerebral ischemia. Proc Natl Acad Sci U S A. 2019;116(20):10019\u201324.","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"1","key":"1993_CR13","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1471-4159.2010.06759.x","volume":"114","author":"SB Matousek","year":"2010","unstructured":"Matousek SB, Hein AM, Shaftel SS, Olschowka JA, Kyrkanides S, O'Banion MK. Cyclooxygenase-1 mediates prostaglandin E(2) elevation and contextual memory impairment in a model of sustained hippocampal interleukin-1beta expression. J Neurochem. 2010;114(1):247\u201358.","journal-title":"J Neurochem."},{"issue":"5","key":"1993_CR14","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1096\/fj.07-9411com","volume":"22","author":"SH Choi","year":"2008","unstructured":"Choi SH, Langenbach R, Bosetti F. Genetic deletion or pharmacological inhibition of cyclooxygenase-1 attenuate lipopolysaccharide-induced inflammatory response and brain injury. FASEB J. 2008;22(5):1491\u2013501.","journal-title":"FASEB J."},{"issue":"38","key":"1993_CR15","doi-asserted-by":"publisher","first-page":"15248","DOI":"10.1523\/JNEUROSCI.6361-11.2013","volume":"33","author":"EW Griffin","year":"2013","unstructured":"Griffin EW, Skelly DT, Murray CL, Cunningham C. Cyclooxygenase-1-dependent prostaglandins mediate susceptibility to systemic inflammation-induced acute cognitive dysfunction. J Neurosci. 2013;33(38):15248\u201358.","journal-title":"J Neurosci."},{"issue":"1","key":"1993_CR16","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1097\/WAD.0b013e3181611024","volume":"22","author":"T Gomez-Isla","year":"2008","unstructured":"Gomez-Isla T, Blesa R, Boada M, Clarimon J, Del Ser T, Domenech G, et al. A randomized, double-blind, placebo controlled-trial of triflusal in mild cognitive impairment: the TRIMCI study. Alzheimer disease and associated disorders. 2008;22(1):21\u20139.","journal-title":"Alzheimer disease and associated disorders."},{"issue":"2","key":"1993_CR17","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1002\/cne.21144","volume":"500","author":"C Gargini","year":"2007","unstructured":"Gargini C, Terzibasi E, Mazzoni F, Strettoi E. Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: a morphological and ERG study. J Comp Neurol. 2007;500(2):222\u201338.","journal-title":"J Comp Neurol."},{"issue":"43","key":"1993_CR18","doi-asserted-by":"publisher","first-page":"18706","DOI":"10.1073\/pnas.1007644107","volume":"107","author":"E Strettoi","year":"2010","unstructured":"Strettoi E, Gargini C, Novelli E, Sala G, Piano I, Gasco P, et al. Inhibition of ceramide biosynthesis preserves photoreceptor structure and function in a mouse model of retinitis pigmentosa. Proc Natl Acad Sci U S A. 2010;107(43):18706\u201311.","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"4","key":"1993_CR19","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.tips.2009.01.002","volume":"30","author":"SH Choi","year":"2009","unstructured":"Choi SH, Aid S, Bosetti F. The distinct roles of cyclooxygenase-1 and -2 in neuroinflammation: implications for translational research. Trends Pharmacol Sci. 2009;30(4):174\u201381.","journal-title":"Trends Pharmacol Sci."},{"issue":"6","key":"1993_CR20","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1097\/01.fjc.0000187174.67661.67","volume":"46","author":"EH Tang","year":"2005","unstructured":"Tang EH, Ku DD, Tipoe GL, Feletou M, Man RY, Vanhoutte PM. Endothelium-dependent contractions occur in the aorta of wild-type and COX2-\/- knockout but not COX1-\/- knockout mice. J Cardiovasc Pharmacol. 2005;46(6):761\u20135.","journal-title":"J Cardiovasc Pharmacol."},{"issue":"12","key":"1993_CR21","doi-asserted-by":"publisher","first-page":"5287","DOI":"10.1167\/iovs.17-22096","volume":"58","author":"K Wang","year":"2017","unstructured":"Wang K, Peng B, Xiao J, Weinreb O, Youdim MBH, Lin B. Iron-chelating drugs enhance cone photoreceptor survival in a mouse model of retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2017;58(12):5287\u201397.","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"1993_CR22","doi-asserted-by":"publisher","first-page":"7601","DOI":"10.1038\/srep07601","volume":"4","author":"K Wang","year":"2014","unstructured":"Wang K, Xiao J, Peng B, Xing F, So KF, Tipoe GL, et al. Retinal structure and function preservation by polysaccharides of wolfberry in a mouse model of retinal degeneration. Scientific reports. 2014;4:7601.","journal-title":"Scientific reports."},{"issue":"7","key":"1993_CR23","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","volume":"169","author":"H Keren-Shaul","year":"2017","unstructured":"Keren-Shaul H, Spinrad A, Weiner A, Matcovitch-Natan O, Dvir-Szternfeld R, Ulland TK, et al. A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease. Cell. 2017;169(7):1276\u201390 e17.","journal-title":"Cell."},{"issue":"6","key":"1993_CR24","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/j.jcyt.2016.03.001","volume":"18","author":"Z Li","year":"2016","unstructured":"Li Z, Zeng Y, Chen X, Li Q, Wu W, Xue L, et al. Neural stem cells transplanted to the subretinal space of rd1 mice delay retinal degeneration by suppressing microglia activation. Cytotherapy. 2016;18(6):771\u201384.","journal-title":"Cytotherapy."},{"issue":"12","key":"1993_CR25","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1038\/s41419-018-1198-1","volume":"9","author":"B Lin","year":"2018","unstructured":"Lin B, Xiong G, Yang W. Ribosomal protein S6 kinase 1 promotes the survival of photoreceptors in retinitis pigmentosa. Cell death & disease. 2018;9(12):1141.","journal-title":"Cell death & disease."},{"issue":"6","key":"1993_CR26","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1016\/j.cell.2010.02.016","volume":"140","author":"CK Glass","year":"2010","unstructured":"Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010;140(6):918\u201334.","journal-title":"Cell."},{"issue":"3","key":"1993_CR27","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.exer.2008.11.022","volume":"88","author":"B Lin","year":"2009","unstructured":"Lin B, Masland RH, Strettoi E. Remodeling of cone photoreceptor cells after rod degeneration in rd mice. Exp Eye Res. 2009;88(3):589\u201399.","journal-title":"Exp Eye Res."},{"key":"1993_CR28","doi-asserted-by":"publisher","first-page":"8936","DOI":"10.1523\/JNEUROSCI.18-21-08936.1998","volume":"18","author":"CJ Jeon","year":"1998","unstructured":"Jeon CJ, Strettoi E, Masland RH. The major cell populations of the mouse retina. J Neurosci. 1998;18:8936.","journal-title":"J Neurosci."},{"issue":"9","key":"1993_CR29","doi-asserted-by":"publisher","first-page":"4042","DOI":"10.1167\/iovs.05-1627","volume":"47","author":"SF Nilsson","year":"2006","unstructured":"Nilsson SF, Drecoll E, Lutjen-Drecoll E, Toris CB, Krauss AH, Kharlamb A, et al. The prostanoid EP2 receptor agonist butaprost increases uveoscleral outflow in the cynomolgus monkey. Invest Ophthalmol Vis Sci. 2006;47(9):4042\u20139.","journal-title":"Invest Ophthalmol Vis Sci."},{"issue":"2","key":"1993_CR30","doi-asserted-by":"publisher","first-page":"234","DOI":"10.18632\/aging.100021","volume":"1","author":"SH Choi","year":"2009","unstructured":"Choi SH, Bosetti F. Cyclooxygenase-1 null mice show reduced neuroinflammation in response to beta-amyloid. Aging. 2009;1(2):234\u201344.","journal-title":"Aging."},{"issue":"44","key":"1993_CR31","doi-asserted-by":"publisher","first-page":"10180","DOI":"10.1523\/JNEUROSCI.3591-05.2005","volume":"25","author":"X Liang","year":"2005","unstructured":"Liang X, Wang Q, Hand T, Wu L, Breyer RM, Montine TJ, et al. Deletion of the prostaglandin E2 EP2 receptor reduces oxidative damage and amyloid burden in a model of Alzheimer's disease. J Neurosci. 2005;25(44):10180\u20137.","journal-title":"J Neurosci."}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01993-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-020-01993-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01993-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T17:44:31Z","timestamp":1698255871000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-020-01993-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,15]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1993"],"URL":"https:\/\/doi.org\/10.1186\/s12974-020-01993-0","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,15]]},"assertion":[{"value":"14 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"306"}}