Therapeutic Potential of Emricasan, a Pan-Caspase Inhibitor, in Reducing Cell Death and Extracellular Matrix Accumulation in Fuchs Endothelial Corneal Dystroph
This RNA-Seq dataset captures transcriptomic changes in the corneal endothelium of Col8a2Q455K/Q455K mice, a model of early-onset Fuchs endothelial corneal dystrophy (FECD), following treatment with the pan-caspase inhibitor emricasan. The experiment compared corneal endothelial cells from 28-week-old mice receiving twice-daily 0.1% emricasan eye drops (n=3) versus vehicle control (n=3) from 8 to 28 weeks of age. Differential expression analysis identified 1,345 differentially expressed genes (455 upregulated, 890 downregulated; |Log2FC| = 1.0, P < 0.05) in emricasan-treated versus control mice. Gene ontology and pathway analyses revealed significant changes in pathways related to ECM production, cell death, and cellular morphology. These transcriptomic changes correlate with the observed improvement in endothelial cell density, hexagonality, and reduction in guttae formation in emricasan-treated mice, providing molecular insights into how caspase inhibition may provide therapeutic benefit in FECD by modulating both apoptotic and ECM production pathways. Overall design: RNA-seq analysis of corneal endothelium from Col8a2Q455K/Q455K mice treated with 0.1% emricasan eye drops vs vehicle control