2023 Fiscal Year Research-status Report
Spatiotemporal metabolomics analysis in the human cornea-on-a-chip for the determination of ocular drug toxicity
| Project/Area Number |
22K14548
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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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| Keywords | Cornea-on-a-chip / Microfluidic / Metabolomic / Drug toxicity |
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| Outline of Annual Research Achievements |
This research aims to identify metabolite markers related to drug toxicity using untargeted metabolomic analysis in a human corneal epithelium-on-a-chip. In the current fiscal year, we successfully investigated the adverse effects of a model drug, diclofenac, a non-steroidal anti-inflammatory drug, in the corneal epithelium-on-a-chip. Through the utilization of untargeted metabolomics and RNA sequencing, we were able to discover metabolite markers and relevant genes associated with diclofenac treatment, such as methyl-2-oxovaleric acid, 3-methyl-2-oxobutanoic acid, and lauroyl-carnitine. This untargeted metabolomic analysis approach in the corneal epithelium-on-a-chip has the potential to be further employed in combination with additional drugs in future.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
The advancement of this research can be credited to the effective implementation of an optimized untargeted metabolomic method for detecting extracellular metabolites in a corneal epithelium-on-a-chip model. Additionally, the capability to validate the system with a drug model has facilitated the discovery of new metabolite markers.
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| Strategy for Future Research Activity |
Based on current progress, we will initially investigate the function of the discovered metabolite markers to determine if they serve as toxic markers when tested with a larger set of drugs. Secondly, we will explore the sensitivity of these markers by examining their correlation with the early onset of relevant gene expression. Additionally, we will concentrate on employing human cells derived from human induced pluripotent stem cells (iPSCs).
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| Causes of Carryover |
Because of the preparation of additional research articles and participation in further conferences for presenting the project results, the applicant anticipates utilizing the budget in the current fiscal year for these purposes.
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