Autoantibody profile of Age-related macular degeneration

2014 Fiscal Year Final Research Report

• Project/Area Number: 24791842
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: MOROHOSHI KEI 東京医科歯科大学, 医学部附属病院, 非常勤講師 (60598415)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 加齢黄斑変性 / 自己抗体 / バイオマーカー / 自己免疫 / 血管新生

Outline of Final Research Achievements

Age-related macular degeneration (AMD) is currently the leading cause of blindness and recent studies have indicated that autoimmunity, in particular, anti-retinal/choroidal autoantibodies affects the development of AMD.
In this study, several novel autoantibodies to metabolic enzymes, including pyruvate kinase M2 (PKM2), aldolase C and glutamine synthetase, were identified by mass spectrometry (LC-MS/MS) and antigen microarray in the sera of AMD patients and IgGs purified from the patients inhibited activity of those enzymes in a dose dependent manner. Moreover, mice with laser-induced choroidal neovascularization (CNV) demonstrated a similar autoantibody profile to AMD patients and increase of PKM2 expression with strong IgG deposition was observed in the CNV lesion. Hence, our data suggested that anti-PKM2 IgG antibody could be a candidate biomarker for AMD and a potential molecular target for novel therapeutic strategies of the disease.

Free Research Field

眼科学