Development of new treatment for retinal edema and fibrosis targeting AM-RAMP2

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H06725
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Ophthalmology
• Research Institution: Shinshu University
• Principal Investigator: Imai Akira 信州大学, 学術研究院医学系, 助教(特定雇用) (60807329)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: アドレノメデュリン / RAMP2 / 加齢黄斑変性

Outline of Final Research Achievements

Studies were conducted to investigate the potential of adrenomedullin (AM) and its receptor modulator protein (RAMP2) as a therapeutic target for age-related macular degeneration. In a study using laser induced choroidal neovascularization model (Laser induced CNV model), which is a mouse model of exudative age-related macular degeneration, CNV size and concomitant fibrosis in the retina in AM and RAMP2 knockout mice was confirmed to be expanding. The involvement of epithelial foliar metastasis (EMT) in retinal fibrosis has been reported, and the role of AM-RAMP2 in EMT was examined. It has been suggested that AM suppresses EMT in retinal pigment epithelial cells and is a target for fibrotic treatment of AMD.

Free Research Field

加齢黄斑変性

Academic Significance and Societal Importance of the Research Achievements

加齢黄斑変性は我が国の中途失明原因の上位を占める。現在、抗VEGF薬による治療が滲出性加齢黄斑変性に対して有効性が示され、臨床応用が確立されている。一方で、滲出が改善した後の網膜の線維化や網膜の萎縮を防ぐことは難しく、網膜の線維化を予防できる新たな治療標的が求められている。
アドレノメデュリン（adrenomedullin；AM）は，ヒト褐色細胞腫組織から発見された血管拡張作用を有する生理活性ペプチドである．循環器疾患や 炎症性疾患では産生が増加し，心血管保護作用や抗炎症作用など多彩な生理作用を有する。今回、加齢黄斑変性の治療ターゲットとしてのAMの検討を行う目的で研究を行った。