Proteomics-based identification and validation of novel plasma biomarkers phospholipid transfer protein and mannan-binding lectin serine protease-1 in age-related macular degeneration.
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.
Center for Theragnosis, Korea Institute of Science and Technology, Seoul, Korea.
Hye-Jung
HJ
Kim
Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.|Department of Ophthalmology, Hanyang University College of Medicine, Hanyang University Hospital, Seoul, Korea.
Seong Joon
SJ
Ahn
Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Se Joon
SJ
Woo
Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Hye Kyoung
HK
Hong
Center for Theragnosis, Korea Institute of Science and Technology, Seoul, Korea.
Eui Jin
EJ
Suh
Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.|Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
Jeeyun
J
Ahn
Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Ji Hyun
JH
Park
Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Na-Kyung
NK
Ryoo
Center for Theragnosis, Korea Institute of Science and Technology, Seoul, Korea.
Ji Eun
JE
Lee
Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea.|Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea.|Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul, Korea.
Ki Woong
KW
Kim
Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Kyu Hyung
KH
Park
Center for Theragnosis, Korea Institute of Science and Technology, Seoul, Korea.
Cheolju
C
Lee
D015415:Biomarkers / Q000097:blood*; D005260:Female; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D049294:Phospholipid Transfer Proteins / Q000097:blood*; D040901:Proteomics
D015415:Biomarkers; D049294:Phospholipid Transfer Proteins; D050606:Mannose-Binding Protein-Associated Serine Proteases