Elucidation of pathogenesis in vascular abnormality of ocular surface in autoimmune diseases and development of new therapeutic intervention

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18855
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Keio University
• Principal Investigator: HAYASHI Isami 慶應義塾大学, 医学部(信濃町), 助教 (00837445)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 慢性移植片対宿主病 / 自己免疫疾患 / 眼表面血管異常 / エクソソーム

Outline of Final Research Achievements

We perfomed histopathological examination of blood vessels and meibomian glands in mouse models of chronic graft-versus-host disease (cGVHD) after hematopoietic stem cell transplantation, and revealed morphological abnormalities such as vasodilatation, tortuosity, and hyperplasia. We reported our research results in an academic journal(Yang F, Hayashi I, et al Ocul Surf. 2022).
In addition, we perfomed immunostaining with exosome-related antibodies on lacrimal gland tissue sections of cGVHD model mice, and found that exosomes localize to the vascular endothelium. Furthermore, after extracting exosomes from the serum of cGVHD model mice using an automatic fraction collector, we analyzed their size and concentration, and found that the mean particle size was significantly larger in the cGVHD group than in the control group.
Based on the above results, we are searching for new therapeutic targets for this disease.

Free Research Field

眼科学

Academic Significance and Societal Importance of the Research Achievements

自己免疫疾患および慢性GVHDの症例には高度なマイボーム腺機能不全やドライアイが高頻度に合併し、眼瞼に多彩な血管異常を伴う場合が多く認められる。本研究ではcGVHDの病態における血管異常の解明のため、モデルマウスを使用した病理組織学的な検討を行なった。
またcGVHDに関連した眼表面の線維化には血液由来の線維芽細胞が関与することが知られ、この細胞はエクソソーム分泌により血管新生を促進することから、エクソソームが病態形成に重要な役割を果たしている可能性に着想し研究を実施した。根治的な標準治療が存在しない本疾患に対して、エクソソームが新たな治療標的となる可能性がある。