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

Area of Science:

• Ophthalmology
• Cell Biology
• Biochemistry

Background:

• Fuchs' endothelial corneal dystrophy (FECD) is a primary cause of corneal endothelial dysfunction.
• Understanding the molecular mechanisms underlying FECD is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the protective effects of taurochenodeoxycholic acid (TCDCA) in FECD.
• To elucidate the underlying mechanism of TCDCA's action in corneal endothelial cells.

Main Methods:

• Quantification of TCDCA levels in aqueous humor of FECD patients and a mouse model.
• Evaluation of corneal endothelial cell morphology and function using OCT and ZO-1 staining.
• In vitro assessment of TCDCA's effects on cell viability, mitochondrial function, ATP, and ROS in human corneal endothelial cells (HCECs).
• RNA sequencing (RNA-seq) and qRT-PCR to explore molecular pathways, with calcium signaling validated in vivo.

Main Results:

• Elevated TCDCA levels were observed in FECD aqueous humor.
• TCDCA treatment ameliorated corneal endothelial dysfunction in a mouse model, improving corneal thickness, cell density, and reducing abnormal cells.
• In vitro, TCDCA enhanced HCEC viability, reduced ROS, restored mitochondrial membrane potential, and increased ATP synthesis in a dose-dependent manner.
• TCDCA's beneficial effects were linked to the activation of the calcium signaling pathway.

Conclusions:

• TCDCA exhibits significant protective effects on corneal endothelial cells in the context of FECD.
• TCDCA represents a potential novel therapeutic target for managing FECD progression.