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Se Joon Woo, Hye-Jung Kim, Jee yun Ahn, Seong Joon Ahn, Hye Kyoung Hong, Na-Kyung Ryoo, Kyu Hyung Park, Cheolju Lee; Identification of three plasma protein biomarkers for age-related macular degeneration using a proteomic analysis. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):798.
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© ARVO (1962-2015); The Authors (2016-present)
To identify plasma protein biomarkers for age-related macular degeneration (AMD) using a large-scale quantitative proteomic discovery procedure.
Plasma proteomes from 20 exudative AMD patients and 20 healthy control patients were comparatively profiled by 4-dimensional liquid chromatography-tandem mass spectrometry (LC-MS/MS). Proteins existing at statistically different levels were validated by enzyme-linked immunosorbent assay (ELISA) and western blotting in 233 and 160 case-controlled samples.
Out of 320 proteins identified, 38 proteins were identified to be differentially expressed in AMD using a 4D protein profiling method. Further validation revealed vinculin, phospholipid transfer protein (PLTP), and mannose-associated serine protease 1 (MASP1) showed significantly higher concentrations in AMD patient plasma compared to control plasma. The AUC for discriminating between AMD and controls was 0.879 for vinculin (N=233), 0.923 for PLTP and 0.840 for MASP1 (N=160). However, the three plasma biomarkers were less useful in discriminating early from late AMD (AUC<0.750). A proteo-genomic combination model using vinculin and two known risk genotypes in ARMS2 and CFH genes additionally provided excellent discrimination of AMD from controls (AUC = 0.916). Additionally, vinculin was strongly expressed in retinal pigment epithelial cells of human eyes, and its expression was elevated when exposed to oxidative stress in vitro.
Vinculin, PLTP, and MASP1 were identified as potential plasma biomarkers for AMD. The early detection of AMD using novel plasma biomarkers may enable timely treatment and vision preservation in the elderly.
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