Elucidation on pathophysiology of immune-mediated dry eye disease by depleting senolytic reagents

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09752
• 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: Keio University
• Principal Investigator: OGAWA Yoko 慶應義塾大学, 医学部(信濃町), 講師(非常勤) (30160774)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ドライアイ / 老化細胞 / 老化細胞除去剤 / 移植片対宿主病 / 眼免疫 / T細胞 / マクロファージ

Outline of Final Research Achievements

Using a mouse GVHD model, we have shown that the infiltration of senescent cells and the cytokines associated with the senescence-associated secretory phenotype (SASP) secreted by these cells are involved in autoimmune-like inflammation and fibrosis in target organs such as the lacrimal glands and ocular surface. We found senescent T cells, B cells and macrophages in ocular GVHD in mice. We investigated and found T cell temporal changes and exibited exhausted T cells and elevation of sensencent T cells in early stage and before oneset of ocular GVHD using spleen cells from this mouse GVHD model.We also elucidated the molecular basis of SASP in ocular GVHD and examined various senolytic agents for their effects.

Free Research Field

眼科

Academic Significance and Societal Importance of the Research Achievements

免疫老化を軸に考えたGVHDによるドライアイおよび全身GVHDに対し抗加齢治療として全く新しい観点からすすめる研究はこれまでになく、学術的意義が高いと考える。本研究成果は、GVHDの病態が自己免疫疾患に類似するため広く自己免疫疾患による重症ドライアイの病態解明と抗加齢療法としての観点からの治療法の開発にも繋がる可能性がある。重症ドライアイの疾病予防のみならず老化細胞除去による病態解明が広く加齢性疾患の抑制に繋がり健康寿命の延長に貢献する可能性がある点に社会的意義があると考える。