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dc.contributor.authorArya, Swati
dc.contributor.authorEmri, Eszter
dc.contributor.authorSynowsky, Silvia A.
dc.contributor.authorShirran, Sally L.
dc.contributor.authorBarzegar-Befroei, Neda
dc.contributor.authorPeto, Tunde
dc.contributor.authorBotting, Catherine H.
dc.contributor.authorLengyel, Imre
dc.contributor.authorStewart, Alan J.
dc.date.accessioned2019-03-24T00:38:51Z
dc.date.available2019-03-24T00:38:51Z
dc.date.issued2018-07
dc.identifier252597345
dc.identifier06f0147d-e34d-44b1-80f5-9818ebabe00f
dc.identifier85056278544
dc.identifier000436528900003
dc.identifier.citationArya , S , Emri , E , Synowsky , S A , Shirran , S L , Barzegar-Befroei , N , Peto , T , Botting , C H , Lengyel , I & Stewart , A J 2018 , ' Quantitative analysis of hydroxyapatite-binding plasma proteins in genotyped individuals with late-stage age-related macular degeneration ' , Experimental Eye Research , vol. 172 , pp. 21-29 . https://doi.org/10.1016/j.exer.2018.03.023en
dc.identifier.issn0014-4835
dc.identifier.otherORCID: /0000-0003-3516-3507/work/43149681
dc.identifier.otherORCID: /0000-0003-4580-1840/work/60195809
dc.identifier.otherORCID: /0000-0001-7978-9507/work/61370157
dc.identifier.urihttps://hdl.handle.net/10023/17357
dc.descriptionWe are also grateful to Fight for Sight for financial support (project grant to A.J.S and I.L.; grant ref.: 1586/1587). This research was also supported by “Eye-Risk” a European Union’s Horizon 2020 research and innovation program (grant ref.: 634479), Bill Brown Charitable Trust, MEH Special Trustees and Mercer Fund (I.L). This work was also supported by the Wellcome Trust (grant ref.: 094476/Z/10/Z) for funding the purchase of the TripleTOF 5600 mass spectrometer at the BSRC Mass Spectrometry and Proteomics Facility, University of St Andrews.en
dc.description.abstractAge-related macular degeneration (AMD) is associated with the formation of sub-retinal pigment epithelial (RPE) deposits that block circulatory exchange with the retina. The factors that contribute to deposit formation are not well understood. Recently, we identified the presence of spherular hydroxyapatite (HAP) structures within sub-RPE deposits to which several AMD-associated proteins were bound. This suggested that protein binding to HAP represents a potential mechanism for the retention of proteins in the sub-RPE space. Here we performed quantitative proteomics using Sequential Window Acquisition of all THeoretical fragment-ion spectra-Mass Spectrometry (SWATH-MS) on plasma samples from 23 patients with late-stage neovascular AMD following HAP-binding. Individuals were genotyped for the high risk CFH variant (T1277C) and binding to HAP was compared between wild type and risk variants. From a library of 242 HAP binding plasma proteins (1% false discovery rate), SWATH-MS revealed significant quantitative differences in the abundance of 32 HAP-binding proteins (p<0.05) between the two homozygous groups. The concentrations of six proteins (FHR1, FHR3, APOC4, C4A, C4B and PZP) in the HAP eluted fractions and whole plasma were further analysed using ELISA and their presence in sections from human cadaver eyes was examined using immunofluorescence. All six proteins were found to be present in the RPE/choroid interface, and four of these (FHR1, FHR3, APOC4 and PZP) were associated with spherules in sub-RPE space. This study provides qualitative and quantitative information relating to the degree by which plasma proteins may contribute to sub-RPE deposit formation through binding to HAP spherules and how genetic differences might contribute to deposit formation.
dc.format.extent9
dc.format.extent2135776
dc.language.isoeng
dc.relation.ispartofExperimental Eye Researchen
dc.subjectDrusenen
dc.subjectSub-retinal pigment epithelial depositsen
dc.subjectMineral-protein interactionsen
dc.subjectRetinal diseaseen
dc.subjectQuantitative proteomicsen
dc.subjectQH426 Geneticsen
dc.subjectRC Internal medicineen
dc.subjectDASen
dc.subject.lccQH426en
dc.subject.lccRCen
dc.titleQuantitative analysis of hydroxyapatite-binding plasma proteins in genotyped individuals with late-stage age-related macular degenerationen
dc.typeJournal articleen
dc.contributor.sponsorThe Wellcome Trusten
dc.contributor.sponsorFight for Sighten
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Cellular Medicine Divisionen
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.identifier.doi10.1016/j.exer.2018.03.023
dc.description.statusPeer revieweden
dc.date.embargoedUntil2019-03-24
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0014483517307819#appd001en
dc.identifier.grantnumber094476/Z/10/Zen
dc.identifier.grantnumber1586 / 1587en


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