Proteomics of vitreous in neovascular age-related macular degeneration. (May 2016)

• Record Type: Journal Article
• Authors: Nobl, Matthias; Reich, Michael; Dacheva, Ivanka; Siwy, Justyna; Mullen, William; Schanstra, Joost P.; Choi, Chul Young; Kopitz, Jürgen; Kretz, Florian T.A.; Auffarth, Gerd U.; Koch, Frank; Koss, Michael J.
• Is Part Of: Experimental eye research. Volume 146(2016:May)
• Page Start: 107
• Page End: 117
• Publication Date: 2016-05
• Subjects: Neovascular age-related macular degeneration -- Vitreous humor -- Proteomics -- Biomarker -- Clusterin -- Opticin -- Pigment epithelium-derived factor -- Prostaglandin-H2 d-isomerase; AMD age-related macular degeneration -- AUC area under the curve -- CE capillary electrophoresis -- CE-MS Capillary electrophoresis coupled online to mass spectrometry -- CNV choroidal neovascularization -- CNVwB choroidal neovascularization with bleeding -- CNVw/oB choroidal neovascularization without bleeding -- ELISA Enzyme-linked Immunosorbent Assay -- GO gene ontology -- hCNV hemorrhagic choroidal neovascularization -- LC-MS/MS liquid chromatography coupled online to tandem mass spectrometry -- MS/MS tandem mass spectrometry -- nAMD neovascular age-related macular degeneration -- PEDF pigment epithelium-derived factor -- PH2D prostaglandin-H2 d-isomerase -- ROC receiver operating characteristic -- VEGF vascular endothelial growth factor -- VH vitreous humor; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2016.01.001
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: 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. Highlights: Shotgun proteomics of vitreous revealed changes in age-related macular degeneration. Statistical analysis regarding clinical diagnosis groups was performed. Clusterin and Prostaglandin-H2 d -isomerase may serve as potential future biomarkers. Opticin and PEDF also seem to be involved in the pathophysiology. Results were obtained by using one of the highest sample numbers in literature.