Abstract
Age-related macular degeneration (AMD) is a major cause of severe, progressive visual loss among the elderly. There are currently no established serological markers for the diagnosis of AMD. In this study, we carried out a large-scale quantitative proteomics analysis to identify plasma proteins that could serve as potential AMD biomarkers. We found that the plasma levels of phospholipid transfer protein (PLTP) and mannan-binding lectin serine protease (MASP)-1 were increased in AMD patients relative to controls. The receiver operating characteristic curve based on data from an independent set of AMD patients and healthy controls had an area under the curve of 0.936 for PLTP and 0.716 for MASP-1, revealing excellent discrimination between the two groups. A proteogenomic combination model that incorporated PLTP and MASP-1 along with two known risk genotypes of age-related maculopathy susceptibility 2 and complement factor H genes further enhanced discriminatory power. Additionally, PLTP and MASP-1 mRNA and protein expression levels were upregulated in retinal pigment epithelial cells upon exposure to oxidative stress in vitro. These results indicate that PLTP and MASP-1 can serve as plasma biomarkers for the early diagnosis and treatment of AMD, which is critical for preventing AMD-related blindness.
Highlights
Ophthalmic examination or interpretation of fundus photographs by retinal specialists is the main method for diagnosing Age-related macular degeneration (AMD)
mannan-binding lectin (MBL) serine protease (MASP)-1 showed a less dramatic spectral count ratio of 1.13 (AMD:healthy controls (HCs)), but was examined here owing to its relationship to signalling pathways implicated in AMD development and progression[5,6,7,8]
A western blot analysis of 12 patients randomly selected from each group revealed an upregulation of phospholipid transfer protein (PLTP) and MASP-1 expression in AMD patients relative to controls that was dependent on disease severity (Fig. 2)
Summary
Ophthalmic examination or interpretation of fundus photographs by retinal specialists is the main method for diagnosing AMD. Detection of blood biomarkers can be used as an additional screening tool, since blood tests are typically performed at medical check-ups and do not require specialists such as ophthalmologists. Our group recently identified over 320 plasma proteins—including vinculin—that were differentially expressed between AMD patients and healthy controls (HCs) as potential plasma biomarkers[4]. We report two candidate biomarkers for AMD, phospholipid transfer protein (PLTP) and mannan-binding lectin (MBL) serine protease (MASP)-1. The relationship between plasma PLTP and MASP-1 levels and systemic factors, such as genotype, was analysed. The effect of oxidative stress, which has been linked to AMD, on the expression and/or secretion of PLTP and MASP-1 was examined
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