Therapeutic Potential of Emricasan, a Pan-Caspase Inhibitor, in Reducing Cell Death and Extracellular Matrix Accumulation in Fuchs Endothelial Corneal Dystrophy

Fujimoto 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 AS, Koizumi N, Okumura N (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Cells MDPI

Book Volume: 14

Article Number: 498

Journal Issue: 7

DOI: 10.3390/cells14070498

Abstract

Fuchs endothelial corneal dystrophy (FECD) is a progressive disorder characterized by endothelial cell loss and excessive extracellular matrix (ECM) accumulation leading to corneal dysfunction. Emricasan, a pan-caspase inhibitor, was investigated for its therapeutic potential in suppressing these pathological changes. Patient-derived FECD cells and stress-induced cell models were treated with emricasan to assess its effects on apoptosis and ECM production. Caspase-specific knockdown experiments were performed to identify key mediators. Col8a2Q455K/Q455K mice, model mice of early-onset FECD, received twice-daily administration of 0.1% emricasan eye drops from 8 to 28 weeks of age. Endothelial cell density, hexagonality, cell size variation, and guttae area were evaluated by contact specular microscopy, while transcriptomic changes were analyzed via RNA sequencing. Emricasan effectively reduced apoptosis and ECM production in vitro by selectively inhibiting caspase-7 without affecting canonical TGF-β signaling. In vivo, emricasan-treated mice exhibited significantly higher endothelial cell density, improved hexagonality, and reduced variation in cell size compared with controls. Transcriptome analysis revealed distinct gene expression changes in the corneal endothelium following emricasan treatment. These findings suggest that emricasan exerts dual protective effects by inhibiting caspase-7-mediated ECM accumulation and broadly suppressing apoptosis, highlighting its potential as a pharmacological therapy for FECD.

Authors with CRIS profile

Theofilos Tourtas Lehrstuhl für Augenheilkunde Ursula Schlötzer-Schrehardt Medizinische Fakultät Friedrich Kruse Lehrstuhl für Augenheilkunde

Involved external institutions

Doshisha University / 同志社大学 JP Japan (JP) ActualEyes Inc. JP Japan (JP) Osaka University / 大阪大学 JP Japan (JP) University of Virginia (UVA) US United States (USA) (US)

How to cite

APA:

Fujimoto, S., Endo, M., Tonomura, S., Tsuji, F., Haraguchi, H., Hasegawa, K.,... 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). https://doi.org/10.3390/cells14070498

MLA:

Fujimoto, Sohya, et al. "Therapeutic Potential of Emricasan, a Pan-Caspase Inhibitor, in Reducing Cell Death and Extracellular Matrix Accumulation in Fuchs Endothelial Corneal Dystrophy." Cells 14.7 (2025).

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