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