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Matthias Nobl, Michael Reich, Ivanka Dacheva, Frank H J Koch, Gerd Auffarth, Michael J Koss; Proteomics of Vitreous Humor in Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):817.
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© ARVO (1962-2015); The Authors (2016-present)
Pathogenesis of Age-related Macular Degeneration (AMD) is a complex, poorly understood interaction of multiple factors. We performed a clinical-experimental study to identify potential future biomarkers and new targets of therapy.
Vitreous samples of patients with AMD (sample group, n=108) or idiopathic floaters (control group, n=26) were analyzed. Patients with systemic diabetes, nephropathy, uncontrolled hypertension or diabetic retinopathy were excluded. Samples were taken via a 23 gauge single-site core vitrectomy. After tryptic digestion analysis was performed using capillary electrophoresis coupled online to a time-of-flight mass spectrometer, as well as tandem mass spectrometry. Significant peptides were determined by comparing AMD-samples with samples of the controls and then matched to corresponding proteins. Gene Ontology-Terms (GO-Terms) were assigned to every IPI number via WebGestalt (WEB-base Gene SeT AnaLysis Toolkit). Three main categories were formed: Biological Process, Cellular Component and Molecular Function. For statistical analysis Wilcoxon-Mann-Whitney Test was used. A P value of α<0.05 was considered statistically significant.
In our analysis 878 successfully sequenced peptides were detected, relating to 136 proteins. 50 proteins, composed of 116 peptides, were expressed significantly different between sample and control group (P=3,48E-8 to 4,91E-2). 42 proteins could be analyzed via WebGestalt. In the following most frequent GO-Terms of the three formed main categories are listed. Biological Process: response to stimulus (n=33), multicellular organismal process (33), biological regulation (28). Cellular component: extracellular space (23), membrane-enclosed lumen (17), extracellular matrix (13). Molecular Function: protein binding (26), structural molecule activity (14), enzyme regulator activity (13).
In this descriptive study we could confirm up- or down regulated proteins in patients with AMD by using one of the highest number of samples in literature. Proteins assigned to the most common GO-Terms may have an important function in the pathogenesis of AMD.
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