{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:40:34Z","timestamp":1789044034975,"version":"build-2803163510"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":250,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although the pathogenesis of choroidal neovascularization (CNV) is largely unknown in age-related macular degeneration (AMD), inflammasomes may contribute to CNV development and progression. To understand the role NLRP3 inflammasomes in CNV, we used Ccr2RFPCx3cr1GFP dual-reporter mice and immunostaining techniques to confirm localization of NLRP3 inflammasomes in the laser-induced CNV (LCNV) lesions. Confocal microscopy was used to image and quantify LCNV volumes. MCC950 was used as NLRP3 inhibitor. ELISA and quantitative RT-PCR were used to confirm the activation of NLRP3 by monitoring the expression of IL-1\u03b2 protein and mRNA in choroidal tissues from LCNV mice. In addition, NLRP3 (\u2212\/\u2212) LCNV mice were used to investigate whether NLRP3 inflammasomes contribute to the development of LCNV lesions. We observed that red fluorescent protein (RFP)\u2013positive monocyte-derived macrophages and GFP-positive microglia-derived macrophages, in addition to other cell types, were localized in LCNV lesions at day 7 post\u2013laser injury. In addition, NLRP3 inflammasomes are associated with LCNV lesions. Inhibition of NLRP3 inflammasomes, using MCC950, caused an increased Ccr2RFP-positive macrophages, Cx3cr1GFP-positive microglia, and other cells, resulting in an increase in total lesion size. NLRP3 (\u2212\/\u2212) LCNV mice showed significantly increased lesion size compared with age-matched controls. Inhibition of NLRP3 resulted in decreased IL-1\u03b2 mRNA and protein expression in the choroidal tissues, suggesting that increased lesion size may not be directly related to IL-1\u03b2.<\/jats:p>","DOI":"10.4049\/immunohorizons.2400025","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T08:44:29Z","timestamp":1716367469000},"page":"363-370","source":"Crossref","is-referenced-by-count":5,"title":["Role of NLRP3 Inflammasomes in Monocyte and Microglial Recruitments in Choroidal Neovascularization"],"prefix":"10.1093","volume":"8","author":[{"given":"Blake W","family":"Dieckmann","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4355-3089","authenticated-orcid":false,"given":"Marcell E","family":"Paguaga","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary W","family":"McCollum","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8070-5841","authenticated-orcid":false,"given":"John S","family":"Penn","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5611-9666","authenticated-orcid":false,"given":"M D Imam","family":"Uddin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine , Nashville, TN"},{"name":"Department of Biomedical Engineering, Vanderbilt University School of Engineering , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,22]]},"reference":[{"key":"2025010608551959700_r1","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/S0140-6736(18)31550-2","article-title":"Age-related macular degeneration","volume":"392","author":"Mitchell","year":"2018","journal-title":"Lancet"},{"key":"2025010608551959700_r2","doi-asserted-by":"crossref","first-page":"E106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. Health"},{"key":"2025010608551959700_r3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41572-021-00265-2","article-title":"Age-related macular degeneration","volume":"7","author":"Fleckenstein","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"2025010608551959700_r4","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1167\/iovs.12-10655","article-title":"NLRP3 inflammasome activation in retinal pigment epithelial cells by lysosomal destabilization: implications for age-related macular degeneration","volume":"54","author":"Tseng","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2025010608551959700_r5","doi-asserted-by":"crossref","first-page":"1047791","DOI":"10.3389\/fmed.2022.1047791","article-title":"A novel optical imaging probe for targeted visualization of NLRP3 inflammasomes in a mouse model of age-related macular degeneration","volume":"9","author":"Paguaga","year":"2023","journal-title":"Front. Med. (Lausanne)"},{"key":"2025010608551959700_r6","doi-asserted-by":"crossref","first-page":"3328","DOI":"10.3390\/ijms20133328","article-title":"The NLRP3 inflammasome: an overview of mechanisms of activation and regulation","volume":"20","author":"Kelley","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"2025010608551959700_r7","doi-asserted-by":"crossref","first-page":"e60194","DOI":"10.7554\/eLife.60194","article-title":"Distinct effects of complement and of NLRP3- and non-NLRP3 inflammasomes for choroidal neovascularization","volume":"9","author":"Malsy","year":"2020","journal-title":"Elife"},{"key":"2025010608551959700_r8","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.celrep.2013.08.002","article-title":"NLRP3 inflammasome blockade inhibits VEGF-A-induced age-related macular degeneration","volume":"4","author":"Marneros","year":"2013","journal-title":"Cell Rep."},{"key":"2025010608551959700_r9","doi-asserted-by":"crossref","first-page":"20636","DOI":"10.1038\/srep20636","article-title":"Fate mapping reveals that microglia and recruited monocyte-derived macrophages are definitively distinguishable by phenotype in the retina","volume":"6","author":"O\u2019Koren","year":"2016","journal-title":"Sci. Rep."},{"key":"2025010608551959700_r10","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s12974-015-0408-3","article-title":"Expression pattern of Ccr2 and Cx3cr1 in inherited retinal degeneration","volume":"12","author":"Kohno","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"2025010608551959700_r11","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.mam.2012.06.003","article-title":"Animal models of age related macular degeneration","volume":"33","author":"Pennesi","year":"2012","journal-title":"Mol. Aspects Med."},{"key":"2025010608551959700_r12","first-page":"e53502","article-title":"A mouse model for laser-induced choroidal neovascularization","volume":"106","author":"Shah","year":"2015","journal-title":"J. Vis. Exp."},{"key":"2025010608551959700_r13","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1016\/S0002-9440(10)65753-7","article-title":"Targeted disruption of the FGF2 gene does not prevent choroidal neovascularization in a murine model","volume":"153","author":"Tobe","year":"1998","journal-title":"Am. J. Pathol."},{"key":"2025010608551959700_r14","doi-asserted-by":"crossref","first-page":"e13693","DOI":"10.1371\/journal.pone.0013693","article-title":"Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice","volume":"5","author":"Saederup","year":"2010","journal-title":"PLoS One"},{"key":"2025010608551959700_r15","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1084\/jem.20171419","article-title":"Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders","volume":"214","author":"Jiang","year":"2017","journal-title":"J. Exp. Med."},{"key":"2025010608551959700_r16","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nm.3806","article-title":"A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases","volume":"21","author":"Coll","year":"2015","journal-title":"Nat. Med."},{"key":"2025010608551959700_r17","doi-asserted-by":"crossref","first-page":"104265","DOI":"10.1016\/j.mvr.2021.104265","article-title":"Down-expression of the NLRP3 inflammasome delays the progression of diabetic retinopathy","volume":"139","author":"Ge","year":"2022","journal-title":"Microvasc. Res."},{"key":"2025010608551959700_r18","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/s41419-020-03076-7","article-title":"Inhibiting the NLRP3 inflammasome with MCC950 ameliorates retinal neovascularization and leakage by reversing the IL-1beta\/IL-18 activation pattern in an oxygen-induced ischemic retinopathy mouse model","volume":"11","author":"Sui","year":"2020","journal-title":"Cell Death Dis."},{"key":"2025010608551959700_r19","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/nm.2717","article-title":"NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components","volume":"18","author":"Doyle","year":"2012","journal-title":"Nat. Med."},{"key":"2025010608551959700_r20","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.3389\/fimmu.2019.01618","article-title":"IL-1 family members mediate cell death, inflammation and angiogenesis in retinal degenerative diseases","volume":"10","author":"Wooff","year":"2019","journal-title":"Front. Immunol."},{"key":"2025010608551959700_r21","doi-asserted-by":"crossref","first-page":"11737","DOI":"10.1074\/jbc.273.19.11737","article-title":"The human ICAM-2 promoter is endothelial cell-specific in vitro and in vivo and contains critical Sp1 and GATA binding sites","volume":"273","author":"Cowan","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2025010608551959700_r22","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/glia.10031","article-title":"Juxtavascular microglia migrate along brain microvessels following activation during early postnatal development","volume":"37","author":"Grossmann","year":"2002","journal-title":"Glia"},{"key":"2025010608551959700_r23","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/ar.1092320409","article-title":"Macrophage development. 1. Rationale for using Griffonia simplicifolia isolectin B4 as a marker for the line","volume":"232","author":"Sorokin","year":"1992","journal-title":"Anat. Rec."},{"key":"2025010608551959700_r24","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.3390\/cells9102277","article-title":"The impact of the CX3CL1\/CX3CR1 axis in neurological disorders","volume":"9","author":"Pawelec","year":"2020","journal-title":"Cells"},{"key":"2025010608551959700_r25","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1167\/iovs.03-0038","article-title":"Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization","volume":"44","author":"Espinosa-Heidmann","year":"2003","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2025010608551959700_r26","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1167\/iovs.03-0097","article-title":"Macrophage depletion inhibits experimental choroidal neovascularization","volume":"44","author":"Sakurai","year":"2003","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2025010608551959700_r27","doi-asserted-by":"crossref","first-page":"e12660","DOI":"10.1111\/jpi.12660","article-title":"Melatonin attenuates choroidal neovascularization by regulating macrophage\/microglia polarization via inhibition of RhoA\/ROCK signaling pathway","volume":"69","author":"Xu","year":"2020","journal-title":"J. Pineal Res."},{"key":"2025010608551959700_r28","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12974-018-1062-3","article-title":"Evidence for the activation of pyroptotic and apoptotic pathways in RPE cells associated with NLRP3 inflammasome in the rodent eye","volume":"15","author":"Gao","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"2025010608551959700_r29","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1161\/CIRCRESAHA.118.311362","article-title":"NLRP3 inflammasome and the IL-1 pathway in atherosclerosis","volume":"122","author":"Grebe","year":"2018","journal-title":"Circ. Res."},{"key":"2025010608551959700_r30","doi-asserted-by":"crossref","first-page":"100906","DOI":"10.1016\/j.preteyeres.2020.100906","article-title":"Incomplete response to anti-VEGF therapy in neovascular AMD: exploring disease mechanisms and therapeutic opportunities","volume":"82","author":"Mettu","year":"2021","journal-title":"Prog. Retin. Eye Res."}],"container-title":["ImmunoHorizons"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/immunohorizons\/article-pdf\/8\/5\/363\/60187985\/ih2400025.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/immunohorizons\/article-pdf\/8\/5\/363\/60187985\/ih2400025.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T03:56:45Z","timestamp":1736135805000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/immunohorizons\/article\/8\/5\/363\/7820168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,1]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5,1]]}},"URL":"https:\/\/doi.org\/10.4049\/immunohorizons.2400025","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3318233\/v1","asserted-by":"object"}]},"ISSN":["2573-7732"],"issn-type":[{"value":"2573-7732","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,5]]},"published":{"date-parts":[[2024,5,1]]}}}