Analysis of microenvironment of corneal transplantation to elucidate the molecular mechanism of failed adaptation of corneal graft to the host environment

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09955
• 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: Kyoto Prefectural University of Medicine
• Principal Investigator: Morio Ueno 京都府立医科大学, 医学(系)研究科(研究院), 講師 (40426531)
• Co-Investigator(Kenkyū-buntansha): 外園 千恵 京都府立医科大学, 医学(系)研究科(研究院), 教授 (30216585)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 角膜内皮細胞 / 前房水 / 微小環境 / miRNA

Outline of Final Research Achievements

In regenerative medicine, chronic dysfunction of transplanted grafts is caused by their failure of adaptation to the host environment. The mechanism is based on cell competition and cooperation via cellular senescence diffusion pathways by SASP (senescence-associated secretory phenotype), miRNAs, and exosomes. We took corneal endothelium as a model of the failed adaptation, we examined molecular dynamics in aqueous humor which is microenvironment of corneal endothelium to elucidate the mechanism of chronic corneal endothelial failure after corneal transplantation and identified SASP-related cytokines and miRNAs responsible for the mechanism.

Free Research Field

眼科学

Academic Significance and Societal Importance of the Research Achievements

移植医療・再生医療の医療現場において移植直後に生じる急性拒絶反応の制御は部分的に奏功していますが、移植片の長期予後は良好ではありません。死体腎移植では50％生着年数は約8年に留まっていますし、角膜移植の術後に角膜内皮細胞は持続的に減少します。これは、まさに晩期臓器不全であり、本機構の解明並びに修復策はありません。本研究で同定した液性因子を介したドナー/ホスト細胞間の細胞競合・細胞同調に係る分子は角膜移植・角膜内皮再生医療を越えて、再生医療・移植医療全般における晩期臓器不全の機序解明の礎となります。