Arya, S;
Emri, E;
Synowsky, SA;
Shirran, SL;
Barzegar-Befroei, N;
Peto, T;
Botting, CH;
... Stewart, AJ; + view all
(2018)
Quantitative analysis of hydroxyapatite-binding plasma proteins in genotyped individuals with late-stage age-related macular degeneration.
Experimental Eye Research
, 172
pp. 21-29.
10.1016/j.exer.2018.03.023.
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Abstract
Age-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.
| Type: | Article |
|---|---|
| Title: | Quantitative analysis of hydroxyapatite-binding plasma proteins in genotyped individuals with late-stage age-related macular degeneration |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.exer.2018.03.023 |
| Publisher version: | https://doi.org/10.1016/j.exer.2018.03.023 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Ophthalmology, Drusen, Sub-retinal pigment epithelial deposits, Mineral-protein interactions, Retinal disease, Quantitative proteomics, COMPLEMENT FACTOR-H, PREGNANCY ZONE PROTEIN, HUMAN BRUCHS MEMBRANE, ALZHEIMERS-DISEASE, SELF-ASSOCIATION, DRUSEN, BIOMARKERS, DEPOSITS, RISK, POLYMORPHISM |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10052578 |
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