| Project/Area Number |
22K14548
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 27040:Biofunction and bioprocess engineering-related
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| Research Institution | Ritsumeikan University |
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Principal Investigator |
ABDALKADER Rodi 立命館大学, 立命館グローバル・イノベーション研究機構, 准教授 (20839964)
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Project Status |
Completed (Fiscal Year 2024)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | human cornea-on-a-chip / metabolomics / drug toxicity / untargeted metabolomic / cornea-on-a-chip / Cornea-on-a-chip / Microfluidic / Metabolomic / Drug toxicity / iPSC |
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| Outline of Research at the Start |
This proposal aims for the development of a dynamic human cornea model in integration with untargeted metabolomics by combining human induced pluripotent stem cells (iPSC), microfluidics technologies, and metabolomics. This approach will allow us to investigate the early toxicity of the ophthalmic drugs through the selection of significant metabolites markers upon drugs exposure.
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| Outline of Final Research Achievements |
In this research study we developed a human corneal epithelium-on-a-chip (CEpOC) in order to model eye disease and to investigate metabolite marker discovery using untargeted metabolomics. Under conditions such as evaporative dry eye, and non-steroidal anti-inflammation drug, diclofenac (DCF). RNA sequencing showed the up-regulation of inflammatory genes such as IL-6, CXCL2 and CCL5. Untargeted LC-MS analysis revealed elevated levels of acylcarnitines and other toxic metabolites (metabotoxins) indicative of mitochondrial stress. This showed that the CEpOC platform can sensitively detect drug-induced molecular alterations and metabolic changes and has value as a potential predictive type of formulation to screen for drug toxicity in the ophthalmic safety studies.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で開発したヒト角膜上皮オンチップ（CEpOC）は、蒸発型ドライアイ環境と薬剤応答を模倣できる高度なin vitroモデルである。RNA-seqと非標的メタボロミクス解析を組み合わせることで、薬剤毒性の早期検出と機序解明が可能となった。本成果は、動物実験に依存しない評価系として3Rs（Replacement, Reduction, Refinement）に貢献し、前臨床段階における安全性評価の精度向上とコスト削減に寄与する。今後、眼科薬開発の促進と高齢化社会における視機能維持、QOL向上への貢献が期待される。
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