Hye-Jung Kim1, Se Joon Woo2, Eui Jin Suh1, Jeeyun Ahn3, Ji Hyun Park2, Hye Kyoung Hong2, Ji Eun Lee1, Seong Joon Ahn2, Duck Jin Hwang4, Ki Woong Kim5, Kyu Hyung Park2, Cheolju Lee6. 1. Theragnosis Research Center, Korea Institute of Science and Technology, Seoul, Korea. 2. Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. 3. 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. 4. Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea Department of Ophthalmology, HanGil Eye Hospital, Incheon, Korea. 5. Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea. 6. Theragnosis Research Center, Korea Institute of Science and Technology, Seoul, Korea Department of Chemical Biology, University of Science and Technology, Daejeon, Korea.
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 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. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
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 AMDpatients 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 AMDpatient 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. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Authors: Anne M Lynch; Brandie D Wagner; Sophie J Weiss; Kirsten M Wall; Alan G Palestine; Marc T Mathias; Frank S Siringo; Jennifer N Cathcart; Jennifer L Patnaik; Daniel W Drolet; Nebojsa Janjic; Naresh Mandava Journal: Transl Vis Sci Technol Date: 2019-01-25 Impact factor: 3.283
Authors: Louise F Porter; Neil Saptarshi; Yongxiang Fang; Sonika Rathi; Anneke I den Hollander; Eiko K de Jong; Simon J Clark; Paul N Bishop; Timothy W Olsen; Triantafillos Liloglou; Venkata R M Chavali; Luminita Paraoan Journal: Clin Epigenetics Date: 2019-01-14 Impact factor: 6.551
Authors: Zulzikry Hafiz Abu Bakar; Hanafi Ahmad Damanhuri; Suzana Makpol; Wan Mohd Aizat Wan Kamaruddin; Nur Fathiah Abdul Sani; Ahmad Imran Zaydi Amir Hamzah; Khairun Nain Nor Aripin; Mohd Dzulkhairi Mohd Rani; Nor Azila Noh; Rosdinom Razali; Musalmah Mazlan; Hamzaini Abdul Hamid; Mazlyfarina Mohamad; Wan Zurinah Wan Ngah Journal: J Alzheimers Dis Date: 2019 Impact factor: 4.472