Therapeutic Potential of Emricasan, a Pan-Caspase Inhibitor, in Reducing Cell Death and Extracellular Matrix Accumulation in Fuchs Endothelial Corneal Dystrophy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethics Statement
2.2. Animals
2.3. Cell Culture and Establishment of Cell Lines
2.4. Annexin V Assay
2.5. Caspase 3/7 Activity Assay
2.6. Immunoblotting
2.7. Immunofluorescence Staining
2.8. qPCR Analysis
2.9. siRNA
2.10. Preparation of Emricasan Eye Drops
2.11. High-Performance Liquid Chromatography
2.12. Contact Specular Microscopy Imaging in Col8a2Q455K/Q455K Mice
2.13. mRNA Library Preparation and Sequencing
2.14. RNA Sequencing Data Analysis
2.15. Multivariate Analysis
2.16. Pathway Analysis
2.17. Statistical Analysis
3. Results
3.1. Caspase Inhibitors Attenuate TGF-β2-Induced Apoptosis in an FECD Cell Model
3.2. Caspase Inhibitors Suppress Various Stress-Induced Apoptosis in CECs
3.3. Emricasan Suppresses TGF-β2-Induced ECM Production and EMT
3.4. Caspase-7 Knockdown Specifically Suppresses TGF-β2-Induced ECM Expression
3.5. Effects of Topical Emricasan Administration on FECD Phenotype in Col8a2Q455K/Q455K Mice
3.6. Effects of Topical Emricasan Administration on Gene Expression in Corneal Endothelium of Col8a2Q455K/Q455K Mice
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Fujimoto, S.; Endo, M.; Tonomura, S.; Tsuji, F.; Haraguchi, H.; Hasegawa, K.; Numao, T.; Izumi, A.; Tourtas, T.; Schlötzer-Schrehardt, U.; et al. Therapeutic Potential of Emricasan, a Pan-Caspase Inhibitor, in Reducing Cell Death and Extracellular Matrix Accumulation in Fuchs Endothelial Corneal Dystrophy. Cells 2025, 14, 498. https://doi.org/10.3390/cells14070498
Fujimoto S, Endo M, Tonomura S, Tsuji F, Haraguchi H, Hasegawa K, Numao T, Izumi A, Tourtas T, Schlötzer-Schrehardt U, et al. Therapeutic Potential of Emricasan, a Pan-Caspase Inhibitor, in Reducing Cell Death and Extracellular Matrix Accumulation in Fuchs Endothelial Corneal Dystrophy. Cells. 2025; 14(7):498. https://doi.org/10.3390/cells14070498
Chicago/Turabian StyleFujimoto, Sohya, Mako Endo, Shigehito Tonomura, Fuuga Tsuji, Hirotaka Haraguchi, Kanna Hasegawa, Taisuke Numao, Ayaka Izumi, Theofilos Tourtas, Ursula Schlötzer-Schrehardt, and et al. 2025. "Therapeutic Potential of Emricasan, a Pan-Caspase Inhibitor, in Reducing Cell Death and Extracellular Matrix Accumulation in Fuchs Endothelial Corneal Dystrophy" Cells 14, no. 7: 498. https://doi.org/10.3390/cells14070498
APA StyleFujimoto, S., Endo, M., Tonomura, S., Tsuji, F., Haraguchi, H., Hasegawa, K., Numao, T., Izumi, A., Tourtas, T., Schlötzer-Schrehardt, U., Kruse, F., Oyama, Y., Ikawa, M., Jun, A. S., Koizumi, N., & Okumura, N. (2025). Therapeutic Potential of Emricasan, a Pan-Caspase Inhibitor, in Reducing Cell Death and Extracellular Matrix Accumulation in Fuchs Endothelial Corneal Dystrophy. Cells, 14(7), 498. https://doi.org/10.3390/cells14070498