Proteomics of vitreous in neovascular age-related macular degeneration

被引:37
作者
Nobl, Matthias [1 ]
Reich, Michael [1 ,2 ]
Dacheva, Ivanka [1 ]
Siwy, Justyna [3 ]
Mullen, William [4 ]
Schanstra, Joost P. [5 ,6 ]
Choi, Chul Young [7 ,8 ,9 ]
Kopitz, Jurgen [10 ]
Kretz, Florian T. A. [1 ]
Auffarth, Gerd U. [1 ,8 ,9 ]
Koch, Frank [11 ]
Koss, Michael J. [1 ,8 ,9 ,12 ]
机构
[1] Heidelberg Univ, Dept Ophthalmol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany
[2] Univ Freiburg, Dept Ophthalmol, Freiburg, Germany
[3] Mosa Diagnost GmbH, Hannover, Germany
[4] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland
[5] INSERM, Inst Cardiovasc & Metab Dis, U1048, Toulouse, France
[6] Univ Toulouse III Paul Sabatier, Toulouse, France
[7] Sungkyunkwan Univ, Sch Med, Kangbuk Samsung Hosp, Dept Ophthalmol, Seoul, South Korea
[8] David J Apple Int Lab Ocular Pathol, Heidelberg, Germany
[9] IVCRC, Heidelberg, Germany
[10] Heidelberg Univ, Dept Pathol, Bergheimer Str 58, D-69115 Heidelberg, Germany
[11] Goethe Univ, Dept Ophthalmol, Frankfurt, Germany
[12] Univ So Calif, Dept Ophthalmol, Los Angeles, CA 90089 USA
关键词
Neovascular age-related macular degeneration; Vitreous humor; Proteomics; Biomarker; Clusterin; Opticin; Pigment epithelium-derived factor; Prostaglandin-H2; D-isomerase; EPITHELIUM-DERIVED FACTOR; MASS-SPECTROMETRY; AQUEOUS-HUMOR; BIOMARKER DISCOVERY; BLADDER-CANCER; HUMAN EYE; PROTEINS; ANGIOGENESIS; OPTICIN; LOCALIZATION;
D O I
10.1016/j.exer.2016.01.001
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Neovascular age-related macular degeneration (nAMD) has been described as a predominantly inflammatory and proangiogenic retino-choroidal disease. Vitreous humor (VH) is the adjacent and accessible compartment which, due to the vicinity to the retina, might best represent changes of protein-based mediators of nAMD. The aim of this clinical-experimental study was to analyze the nAMD associated VH proteome of previously untreated patients whilst taking different groups of nAMD into account, based on their clinical presentation (clinical diagnosis groups). Electrophoresis coupled online to mass spectrometry (CE-MS) as well as liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) were used to analyze VH of 108 nAMD patients and 24 controls with idiopathic floaters. A total of 101 different proteins with at least two unique peptides could be identified. Using a stringent statistical analysis with implementation of the closed test principle, we were able to identify four proteins that may be involved in the pathophysiology of nAMD: Clusterin, opticin, pigment epithelium-derived factor and prostaglandin-H2 D-isomerase. Using independent samples, ROC-Area under the curve was determined proving the validity of the results: Clusterin 0.747, opticin 0.656, pigment epithelium-derived factor 0.514, prostaglandin-H2 D-isomerase 0.712. In addition, validation through ELISA measurements was performed. The identified proteins may serve as potential biomarkers or even targets of therapy for nAMD. (c) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:107 / 117
页数:11
相关论文
共 53 条
[1]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[2]  
Beuckmann CT, 1996, J NEUROSCI, V16, P6119
[3]   Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor/retinal pigment epithelium/Bruch's membrane/choriocapillaris complex [J].
Bhutto, Imran ;
Lutty, Gerard .
MOLECULAR ASPECTS OF MEDICINE, 2012, 33 (04) :295-317
[4]   Relationship between the complement system, risk factors and prediction models in age-related macular degeneration [J].
Bora, Nalini S. ;
Matta, Bharati ;
Lyzogubov, Valeriy V. ;
Bora, Puran S. .
MOLECULAR IMMUNOLOGY, 2015, 63 (02) :176-183
[5]   Prevalence and causes of vision loss in high-income countries and in Eastern and Central Europe: 1990-2010 [J].
Bourne, Rupert R. A. ;
Jonas, Jost B. ;
Flaxman, Seth R. ;
Keeffe, Jill ;
Leasher, Janet ;
Naidoo, Kovin ;
Parodi, Maurizio B. ;
Pesudovs, Konrad ;
Price, Holly ;
White, Richard A. ;
Wong, Tien Y. ;
Resnikoff, Serge ;
Taylor, Hugh R. .
BRITISH JOURNAL OF OPHTHALMOLOGY, 2014, 98 (05) :629-638
[6]   Age-Related Macular Degeneration [J].
Cheung, Lily K. ;
Eaton, Angie .
PHARMACOTHERAPY, 2013, 33 (08) :838-855
[7]   Age-related macular degeneration [J].
Coleman, Hanna R. ;
Chan, Chi-Chao ;
Ferris, Frederick L., III ;
Chew, Emily Y. .
LANCET, 2008, 372 (9652) :1835-1845
[8]   Drusen proteome analysis: An approach to the etiology of age-related macular degeneration [J].
Crabb, JW ;
Miyagi, M ;
Gu, XR ;
Shadrach, K ;
West, KA ;
Sakaguchi, H ;
Kamei, M ;
Hasan, A ;
Yan, L ;
Rayborn, ME ;
Salomon, RG ;
Hollyfield, JG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (23) :14682-14687
[9]   Pigment epithelium-derived factor: A potent inhibitor of angiogenesis [J].
Dawson, DW ;
Volpert, OV ;
Gillis, P ;
Crawford, SE ;
Xu, HJ ;
Benedict, W ;
Bouck, NP .
SCIENCE, 1999, 285 (5425) :245-248
[10]   Mechanisms of disease: Age-related macular degeneration [J].
de Jong, Paulus T. V. M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (14) :1474-1485