Identification of three plasma protein biomarkers for age-related macular degeneration using a proteomic analysis

Abstract

Purpose: To identify plasma protein biomarkers for age-related macular degeneration (AMD) using a large-scale quantitative proteomic discovery procedure.

Methods: 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.

Results: 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.

Conclusions: 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.