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2021 Fiscal Year Final Research Report

Elucidate the drusen formation mechanism using disease-specific iPS cells

Research Project

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Project/Area Number 20K18341
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56060:Ophthalmology-related
Research InstitutionKyoto University

Principal Investigator

INOUE YUMI  京都大学, 医学研究科, 特定研究員 (70867481)

Project Period (FY) 2020-04-01 – 2022-03-31
KeywordsiPS-RPE / 黄斑変性 / 加齢黄斑変性症
Outline of Final Research Achievements

In this study, reproduce the pathological condition using iPS-RPE derived from Macular degeneration patients, then evaluating the morphology, phagocytic ability, and digestive ability of iPS-RPE. Furthermore, examining the relationship with the lipid profile by lipid analysis and the mechanism of drusen formation was elucidated. We could differentiate the Patient-derived iPS-RPE and healthy-derived iPS-RPE, and the protein expression of Fibulin-3 was increased in the Patient-derived iPS-RPE, and the pathological condition of Macular degeneration patients could be reproduced. In the comprehensive lipid analysis, it was found that the intracellular lipid composition differs between the Patient-derived iPS-RPE and healthy-derived iPS-RPE as a result of clustering analysis. It was also found that the intracellular constituent lipids are changed by phagocytosing the extracellular segment of photoreceptor cells.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、大きなドルーゼンを多数持つ患者由来のRPE(iPS-RPE)の脂質プロファイルからドルーゼン形成メカニズムを明らかにすることを目的とした。研究成果ではiPS-RPEで病態を再現することに成功し、脂質解析による貪食した視細胞外節の代謝経路や細胞内の脂質分布の変化を調べることが可能になった。これらの結果からMALの病態を解明することで、ドルーゼン形成のメカニズムを明らかにすることができる。脂質プロファイルからドルーゼン形成との関連を調べる研究はこれまでになく学術的意義は高い。このメカニズムが明らかになることで、ドルーゼン消失の治療法または治療薬の開発の進展が期待でき社会的意義も大きい。

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Published: 2023-01-30   Modified: 2025-01-30  

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