title: Identification of vinculin as a potential plasma marker for age-related macular degeneration.
abstract: OBJECTIVE
  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 four-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 case-controlled samples. Newly discovered plasma biomarkers were further confirmed using in vivo and in vitro experiments.
  
  
  RESULTS
  Out of 320 proteins identified, vinculin, protein S100A9, triosephosphate isomerase, protein S100A8, protein Z-dependent protease inhibitor, C-X-C motif chemokine 7, and tenascin X showed significantly differential expression in AMD patient plasma compared to control plasma. Among these, the area under the curve (AUC) for vinculin was 0.871 for discriminating between exudative AMD and controls (n = 201) and 0.879 for discriminating between AMD and controls (n = 233). A proteogenomic 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). The plasma level of vinculin was not associated with any confounding clinical variables, such as age, smoking, and other comorbidities. 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 was identified as a potential plasma biomarker for AMD. The early detection of AMD using novel plasma biomarkers with genetic modeling may enable timely treatment and vision preservation in the elderly.
authors.affiliation: Theragnosis Research Center, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Se Joon
authors.initials: SJ
authors.lastname: Woo
authors.affiliation: Theragnosis Research Center, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Eui Jin
authors.initials: EJ
authors.lastname: Suh
authors.affiliation: 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.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Hye Kyoung
authors.initials: HK
authors.lastname: Hong
authors.affiliation: Theragnosis Research Center, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Seong Joon
authors.initials: SJ
authors.lastname: Ahn
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea Department of Ophthalmology, HanGil Eye Hospital, Incheon, Korea.
authors.forename: Duck Jin
authors.initials: DJ
authors.lastname: Hwang
authors.affiliation: Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Ki Woong
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Kyu Hyung
authors.initials: KH
authors.lastname: Park
authors.affiliation: Theragnosis Research Center, Korea Institute of Science and Technology, Seoul, Korea Department of Chemical Biology, University of Science and Technology, Daejeon, Korea.
authors.forename: Cheolju
authors.initials: C
authors.lastname: Lee
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008266:Macula Lutea / Q000378:metabolism / Q000473:pathology; D008268:Macular Degeneration / Q000097:blood* / Q000473:pathology; D008297:Male; D040901:Proteomics; D012189:Retrospective Studies; D053719:Tandem Mass Spectrometry; D016596:Vinculin / Q000096:biosynthesis / Q000097:blood*
chemical_list: D015415:Biomarkers; D016596:Vinculin
keywords: 4-dimensional protein profiling; age-related macular degeneration; plasma marker; proteomics; vinculin