Elucidation of the role of innate immunity and application to the clinical use in age-related macular degeneration

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16977
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Nagoya City University
• Principal Investigator: Tomiyasu Taneto 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (70770436)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 脈絡膜新生血管

Outline of Final Research Achievements

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) has been beneficial in improving the visual outcomes in patients with a choroidal neovascularization associated with age-related macular degeneration. However, there are still refractory cases or most patients need multiple injections of anti-VEGF agents. We focused on high-mobility group protein B1 (HMGB1) as a new target in the treatment of CNV. HMGB1 was upregulated around the laser-induced CNV in the RPE-Choroid of the mice. Intravitreal injections of anti-HMGB1 antibody suppressed the laser-induced CNV volume and the leakage from the CNV. In addition, intravitreal injection of anti-HMGB1 antibody suppressed the expression of inflammatory cytokines such as VEGF, interleukin-6, monocyte chemotactic protein-1. Thus, blockade of HMGB1 reduced the expression of such inflammatory cytokines, resulting in suppressing CNV.

Free Research Field

眼科

Academic Significance and Societal Importance of the Research Achievements

加齢黄斑変性は失明の危険性のある疾患で、年々増加傾向にある。加齢黄斑変性の滲出型である脈絡膜新生血管（choroidal neovascularization: CNV）に対しては、血管内皮増殖因子阻害療法が一定の効果をあげているが、充分とは言えない。今回我々は、新たな治療ターゲットとしてhigh-mobility group protein B1: HMGB1に注目した。HMGB1阻害はマウスで実験的に作成したCNV周囲に過剰に発現しており、その阻害によりCNVが縮小した。また、CNV形成に関与する炎症性サイトカインの過剰な発現を抑制することができ、CNV形成に関与することが示された。