Taurochenodeoxycholic Acid Activates Calcium Signaling to Protect Against Fuchs' Endothelial Corneal Dystrophy

Fuchs' endothelial corneal dystrophy (FECD) is the leading cause of corneal endothelial dystrophy. This study aimed to investigate the protective effects and mechanism of taurochenodeoxycholic acid (TCDCA) in FECD.

TCDCA levels were quantified in aqueous humor from patients with FECD and ultraviolet A (UVA)-induced FECD mice. Corneal endothelial cell (CEC) morphology and function were evaluated by optical coherence tomography (OCT) and ZO-1 staining following TCDCA treatment. In vitro, UVA-induced human corneal endothelial cells (HCECs) were treated with TCDCA, and cell viability, mitochondrial membrane potential, ATP, and reactive oxygen species (ROS) levels were measured. RNA sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) were used to explore molecular mechanisms, and the role of Ca²⁺ signaling was validated using the inhibitor 2-APB in vivo.

Analysis of FECD aqueous humor revealed significantly elevated TCDCA levels. In UVA-induced mouse model, TCDCA administration ameliorated corneal endothelial dysfunction, as evidenced by reduced corneal thickness, increased endothelial cell density, and a lower percentage of abnormal cells. Further, in vitro studies revealed a concentration-dependent effect of TCDCA, with 100 µM TCDCA significantly enhancing cell viability, reducing ROS production, restoring mitochondrial membrane potential, and promoting ATP synthesis. RNA-seq and functional studies identified that TCDCA exerts its beneficial effects on corneal endothelial function by activating the calcium signaling pathway.

TCDCA demonstrated a protective effect on corneal endothelial cells during the pathogenesis of FECD. Therefore, TCDCA may be a promising novel therapeutic target for attenuating the progression of FECD.