{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T06:22:22Z","timestamp":1777098142777,"version":"3.51.4"},"reference-count":52,"publisher":"Impact Journals, LLC","issue":"14","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging"],"published-print":{"date-parts":[[2020,7,16]]},"DOI":"10.18632\/aging.103655","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T18:01:30Z","timestamp":1594922490000},"page":"13905-13923","source":"Crossref","is-referenced-by-count":21,"title":["Activation of C-reactive protein proinflammatory phenotype in the blood retinal barrier in vitro: implications for age-related macular degeneration"],"prefix":"10.18632","volume":"12","author":[{"given":"Sara","family":"Romero-V\u00e1zquez","sequence":"first","affiliation":[{"name":"Group of Ocular Inflammation, Clinical and Experimental Studies, Institut d\u2019Investigacions Biom\u00e8diques Agust\u00ed Pi i Sunyer (IDIBAPS), Hospital Cl\u00ednic de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Ad\u00e1n","sequence":"additional","affiliation":[{"name":"Group of Ocular Inflammation, Clinical and Experimental Studies, Institut d\u2019Investigacions Biom\u00e8diques Agust\u00ed Pi i Sunyer (IDIBAPS), Hospital Cl\u00ednic de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Figueras-Roca","sequence":"additional","affiliation":[{"name":"Group of Ocular Inflammation, Clinical and Experimental Studies, Institut d\u2019Investigacions Biom\u00e8diques Agust\u00ed Pi i Sunyer (IDIBAPS), Hospital Cl\u00ednic de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Lloren\u00e7","sequence":"additional","affiliation":[{"name":"Group of Ocular Inflammation, Clinical and Experimental Studies, Institut d\u2019Investigacions Biom\u00e8diques Agust\u00ed Pi i Sunyer (IDIBAPS), Hospital Cl\u00ednic de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Slevin","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Manchester Metropolitan University, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma","family":"Vilahur","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, CiberCV, Institute Carlos III, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Badimon","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, CiberCV, Institute Carlos III, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew D","family":"Dick","sequence":"additional","affiliation":[{"name":"Academic Unit of Ophthalmology, School of Clinical Sciences and School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK"},{"name":"National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blanca","family":"Molins","sequence":"additional","affiliation":[{"name":"Group of Ocular Inflammation, Clinical and Experimental Studies, Institut d\u2019Investigacions Biom\u00e8diques Agust\u00ed Pi i Sunyer (IDIBAPS), Hospital Cl\u00ednic de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"7892","published-online":{"date-parts":[[2020,7,16]]},"reference":[{"key":"1","doi-asserted-by":"publisher","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":"2","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1001\/archopht.122.4.598","article-title":"Current concepts in the pathogenesis of age-related macular degeneration.","volume":"12","author":"Zarbin","year":"2004","journal-title":"Arch Ophthalmol"},{"key":"3","first-page":"1986","article-title":"Quantifying changes in RPE and choroidal vasculature in eyes with age-related macular degeneration.","volume":"4","author":"Lutty","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"4","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/nri3459","article-title":"Immunology of age-related macular degeneration.","volume":"1","author":"Gelfand","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"5","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1038\/nri3547","article-title":"Age-dependent dysregulation of innate immunity.","volume":"1","author":"Montgomery","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"6","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.survophthal.2005.12.001","article-title":"The role of inflammation in the pathogenesis of age-related macular degeneration.","volume":"5","author":"Hageman","year":"2006","journal-title":"Surv Ophthalmol"},{"key":"7","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/eye.2016.177","article-title":"Doyne lecture 2016: intraocular health and the many faces of inflammation.","volume":"3","author":"Dick","year":"2017","journal-title":"Eye (Lond)"},{"key":"8","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.preteyeres.2018.10.003","article-title":"Immune regulation in the aging retina.","volume":"6","author":"Xu","year":"2019","journal-title":"Prog Retin Eye Res"},{"key":"9","doi-asserted-by":"publisher","first-page":"14682","DOI":"10.1073\/pnas.222551899","article-title":"Drusen proteome analysis: an approach to the etiology of age-related macular degeneration.","volume":"9","author":"Hollyfield","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"10","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1006\/exer.2001.1094","article-title":"Complement activation and inflammatory processes in drusen formation and age related macular degeneration.","volume":"7","author":"Anderson","year":"2001","journal-title":"Exp Eye Res"},{"key":"11","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1126\/science.1110359","article-title":"Complement factor H variant increases the risk of age-related macular degeneration.","volume":"30","author":"Pericak-Vance","year":"2005","journal-title":"Science"},{"key":"12","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1126\/science.1110189","article-title":"Complement factor H polymorphism and age-related macular degeneration.","volume":"30","author":"Farrer","year":"2005","journal-title":"Science"},{"key":"13","doi-asserted-by":"publisher","first-page":"48487","DOI":"10.1074\/jbc.R400025200","article-title":"C-reactive protein.","volume":"27","author":"Samols","year":"2004","journal-title":"J Biol Chem"},{"key":"14","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1001\/archopht.123.6.774","article-title":"Progression of age-related macular degeneration: prospective assessment of c-reactive protein, interleukin 6, and other cardiovascular biomarkers.","volume":"12","author":"Rifai","year":"2005","journal-title":"Arch Ophthalmol"},{"key":"15","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.1016\/j.ophtha.2005.07.004","article-title":"Biomarkers of cardiovascular disease as risk factors for age-related macular degeneration.","volume":"11","author":"Swaroop","year":"2005","journal-title":"Ophthalmology"},{"key":"16","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/s0161-5890(01)00042-6","article-title":"Human C-reactive protein: expression, structure, and function.","volume":"3","author":"Volanakis","year":"2001","journal-title":"Mol Immunol"},{"key":"17","doi-asserted-by":"publisher","first-page":"4374","DOI":"10.4049\/jimmunol.1002488","article-title":"Complement regulation at necrotic cell lesions is impaired by the age-related macular degeneration-associated factor-H His402 risk variant.","volume":"18","author":"Zipfel","year":"2011","journal-title":"J Immunol"},{"key":"18","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1096\/fj.06-6722com","article-title":"Cell membranes and liposomes dissociate c-reactive protein (CRP) to form a new, biologically active structural intermediate: mCRP(m).","volume":"2","author":"Zhao","year":"2007","journal-title":"FASEB J"},{"key":"19","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1161\/CIRCRESAHA.108.190611","article-title":"Dissociation of pentameric to monomeric c-reactive protein on activated platelets localizes inflammation to atherosclerotic plaques.","volume":"10","author":"Peter","year":"2009","journal-title":"Circ Res"},{"key":"20","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1161\/CIRCULATIONAHA.113.007124","article-title":"Dissociation of pentameric to monomeric c-reactive protein localizes and aggravates inflammation: in vivo proof of a powerful proinflammatory mechanism and a new anti-inflammatory strategy.","volume":"13","author":"Stark","year":"2014","journal-title":"Circulation"},{"key":"21","doi-asserted-by":"publisher","first-page":"40775","DOI":"10.1074\/jbc.M205378200","article-title":"Loss of pentameric symmetry of c-reactive protein is associated with delayed apoptosis of human neutrophils.","volume":"27","author":"Filep","year":"2002","journal-title":"J Biol Chem"},{"key":"22","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1161\/01.CIR.0000125527.41598.68","article-title":"Conformational rearrangement in c-reactive protein is required for proinflammatory actions on human endothelial cells.","volume":"10","author":"Filep","year":"2004","journal-title":"Circulation"},{"key":"23","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1161\/ATVBAHA.108.174359","article-title":"C-reactive protein isoforms differ in their effects on thrombus growth.","volume":"2","author":"Badimon","year":"2008","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"24","first-page":"835","article-title":"Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease.","volume":"1","author":"Hageman","year":"2000","journal-title":"FASEB J"},{"key":"25","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/s0002-9394(02)01624-0","article-title":"A role for local inflammation in the formation of drusen in the aging eye.","volume":"13","author":"Johnson","year":"2002","journal-title":"Am J Ophthalmol"},{"key":"26","doi-asserted-by":"publisher","first-page":"C244","DOI":"10.1152\/ajpcell.00057.2016","article-title":"C-reactive protein isoforms differentially affect outer blood-retinal barrier integrity and function.","volume":"31","author":"Martorell","year":"2017","journal-title":"Am J Physiol Cell Physiol"},{"key":"27","doi-asserted-by":"publisher","first-page":"22889","DOI":"10.1038\/srep22889","article-title":"Complement factor H binding of monomeric c-reactive protein downregulates proinflammatory activity and is impaired with at risk polymorphic CFH variants.","volume":"6","author":"Dick","year":"2016","journal-title":"Sci Rep"},{"key":"28","doi-asserted-by":"publisher","first-page":"808","DOI":"10.3389\/fimmu.2018.00808","article-title":"C-reactive protein as a therapeutic target in age-related macular degeneration.","volume":"9","author":"Dick","year":"2018","journal-title":"Front Immunol"},{"key":"29","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1002\/path.4766","article-title":"Monomeric c-reactive protein and inflammation in age-related macular degeneration.","volume":"24","author":"Mullins","year":"2016","journal-title":"J Pathol"},{"key":"30","doi-asserted-by":"publisher","first-page":"17456","DOI":"10.1073\/pnas.0606234103","article-title":"Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid.","volume":"10","author":"Johnson","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"31","doi-asserted-by":"publisher","first-page":"1740","DOI":"10.1038\/s41433-018-0170-8","article-title":"Evaluation of serum and ocular levels of membrane attack complex and c-reactive protein in CFH-genotyped human donors.","volume":"3","author":"Mullins","year":"2018","journal-title":"Eye (Lond)"},{"key":"32","doi-asserted-by":"publisher","first-page":"3846","DOI":"10.3390\/ijms19123846","article-title":"The different facades of retinal and choroidal endothelial cells in response to hypoxia.","volume":"1","author":"Andr\u00e9","year":"2018","journal-title":"Int J Mol Sci"},{"key":"33","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/j.healun.2007.04.006","article-title":"Conduct unbecoming: c-reactive protein interactions with a broad range of protein molecules.","volume":"2","author":"Labarrere","year":"2007","journal-title":"J Heart Lung Transplant"},{"key":"34","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1136\/bjo.2010.199216","article-title":"C-reactive protein and complement factor H in aged human eyes and eyes with age-related macular degeneration.","volume":"9","author":"Lutty","year":"2011","journal-title":"Br J Ophthalmol"},{"key":"35","doi-asserted-by":"publisher","first-page":"203","DOI":"10.5551\/jat.3004","article-title":"Chronic CRP-exposure inhibits VEGF-induced endothelial cell migration.","volume":"1","author":"Goetze","year":"2010","journal-title":"J Atheroscler Thromb"},{"key":"36","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1161\/01.cir.0000029802.88087.5e","article-title":"A self-fulfilling prophecy: c-reactive protein attenuates nitric oxide production and inhibits angiogenesis.","volume":"10","author":"Stewart","year":"2002","journal-title":"Circulation"},{"key":"37","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.atherosclerosis.2007.12.046","article-title":"C-reactive protein (CRP) increases VEGF-a expression in monocytic cells via a PI3-kinase and ERK \u00bd signaling dependent pathway.","volume":"20","author":"Ropars","year":"2008","journal-title":"Atherosclerosis"},{"key":"38","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/s13287-016-0377-1","article-title":"C-reactive protein can upregulate VEGF expression to promote ADSC-induced angiogenesis by activating HIF-1\u03b1 via CD64\/PI3k\/Akt and MAPK\/ERK signaling pathways.","volume":"7","author":"Chen","year":"2016","journal-title":"Stem Cell Res Ther"},{"key":"39","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1111\/j.1750-3639.2008.00256.x","article-title":"Modified c-reactive protein is expressed by stroke neovessels and is a potent activator of angiogenesis in vitro.","volume":"2","author":"Krupinski","year":"2010","journal-title":"Brain Pathol"},{"key":"40","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1161\/01.STR.0000217386.37107.be","article-title":"Endogenous expression of c-reactive protein is increased in active (ulcerated noncomplicated) human carotid artery plaques.","volume":"3","author":"Badimon","year":"2006","journal-title":"Stroke"},{"key":"41","doi-asserted-by":"publisher","first-page":"13281","DOI":"10.1038\/srep13281","article-title":"Monomeric c-reactive protein\u2014a key molecule driving development of Alzheimer\u2019s disease associated with brain ischaemia?","volume":"5","author":"Font","year":"2015","journal-title":"Sci Rep"},{"key":"42","doi-asserted-by":"publisher","first-page":"14283","DOI":"10.1074\/jbc.M114.555318","article-title":"Topological localization of monomeric c-reactive protein determines proinflammatory endothelial cell responses.","volume":"28","author":"Ji","year":"2014","journal-title":"J Biol Chem"},{"key":"43","doi-asserted-by":"publisher","first-page":"2469","DOI":"10.1161\/01.ATV.0000241572.05292.fb","article-title":"C-reactive protein decreases interleukin-10 secretion in activated human monocyte-derived macrophages via inhibition of cyclic AMP production.","volume":"2","author":"Jialal","year":"2006","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"44","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1096\/fj.08-116962","article-title":"Monomeric c-reactive protein activates endothelial cells via interaction with lipid raft microdomains.","volume":"2","author":"Wu","year":"2009","journal-title":"FASEB J"},{"key":"45","doi-asserted-by":"publisher","first-page":"C832","DOI":"10.1152\/ajpcell.00405.2005","article-title":"Bipolar assembly of caveolae in retinal pigment epithelium.","volume":"29","author":"Rodriguez-Boulan","year":"2006","journal-title":"Am J Physiol Cell Physiol"},{"key":"46","doi-asserted-by":"publisher","first-page":"8614","DOI":"10.1167\/iovs.11-8021","article-title":"Human retinal pigment epithelium cells as functional models for the RPE in vivo.","volume":"5","author":"Crosson","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"47","doi-asserted-by":"publisher","first-page":"137","DOI":"10.3389\/fnagi.2019.00137","article-title":"Involvement of microRNA-34a in age-related susceptibility to oxidative stress in ARPE-19 cells by targeting the silent mating type information regulation 2 homolog 1\/p66shc pathway: implications for age-related macular degeneration.","volume":"1","author":"Wu","year":"2019","journal-title":"Front Aging Neurosci"},{"key":"48","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.exer.2014.05.003","article-title":"A detailed three-step protocol for live imaging of intracellular traffic in polarized primary porcine RPE monolayers.","volume":"12","author":"Lakkaraju","year":"2014","journal-title":"Exp Eye Res"},{"key":"49","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1136\/bjo.2004.063602","article-title":"Isolation, culture, and characterisation of human macular inner choroidal microvascular endothelial cells.","volume":"8","author":"Amoaku","year":"2005","journal-title":"Br J Ophthalmol"},{"key":"50","doi-asserted-by":"publisher","first-page":"107751","DOI":"10.1016\/j.exer.2019.107751","article-title":"Shear stress modulates inner blood retinal barrier phenotype.","volume":"18","author":"Martorell","year":"2019","journal-title":"Exp Eye Res"},{"key":"51","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1111\/j.1365-2567.2006.02516.x","article-title":"Structural and functional comparison of native pentameric, denatured monomeric and biotinylated c-reactive protein.","volume":"12","author":"van den Berg","year":"2007","journal-title":"Immunology"},{"key":"52","doi-asserted-by":"publisher","first-page":"511","DOI":"10.3389\/fimmu.2018.00511","article-title":"An ELISA assay for quantifying monomeric c-reactive protein in plasma.","volume":"9","author":"Wu","year":"2018","journal-title":"Front Immunol"}],"container-title":["Aging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.aging-us.com\/lookup\/doi\/10.18632\/aging.103655","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T20:48:47Z","timestamp":1599079727000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.aging-us.com\/lookup\/doi\/10.18632\/aging.103655"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,16]]},"references-count":52,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2020,7,31]]}},"alternative-id":["103655","32673285"],"URL":"https:\/\/doi.org\/10.18632\/aging.103655","relation":{},"ISSN":["1945-4589"],"issn-type":[{"value":"1945-4589","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,16]]}}}