Role and clinical application of exosome in corneal transplantation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09730
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Nihon University
• Principal Investigator: YAMAGAMI Satoru 日本大学, 医学部, 教授 (10220245)
• Co-Investigator(Kenkyū-buntansha): 林 孝彦 日本大学, 医学部, 准教授 (20527931)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 角膜移植 / 細胞外小胞

Outline of Final Research Achievements

We aimed to investigate the role of extracellular vesicles in a mouse corneal transplantation model. We used transmission electron microscopy to visualize the drainage of extracellular vesicles derived from the graft into the cervical lymph nodes using gold colloids as markers. Lymph node cells sensitized to graft-derived extracellular vesicles exhibited high proliferation when exposed to cultured corneal stromal cells in a mixed lymphocyte reaction. Notably, extracellular vesicles carrying graft-derived IA antigens were detected in cervical lymph nodes within a maximum of 6 h postoperatively. Moreover, administration of extracellular vesicles extracted from cultured corneal stromal cells significantly reduced the graft survival rate. These findings provide the first evidence of a semi-direct pathway in which graft-derived extracellular vesicles are captured in cervical lymph nodes and contribute to the promotion of allograft rejection in corneal transplantation.

Free Research Field

眼科学

Academic Significance and Societal Importance of the Research Achievements

角膜移植に関連する主な抗原提示経路は2つある。直接認識は、ドナー角膜由来の樹状細胞が直接レシピエントの頸部リンパ節に流入し抗原を提示する経路で、間接経路による抗原提示は、移植片のペプチドを介して、ドナー角膜の抗原提示細胞（APC）を介してT細胞に抗原を提示するものである。本研究は、角膜移植片由来の細胞外小胞が宿主への抗原提示に役割を果たしていることを、in vivoとin vitroの両方で証明したものである。１００年の歴史を持つ角膜移植の常識を塗り替えた論文である。