Alleviation of Endoplasmic Reticulum Stress Enhances Human Corneal Epithelial Cell Viability under Hyperosmotic...

Area of Science:

• Ophthalmology
• Cell Biology
• Molecular Biology

Background:

• Tear hyperosmolarity is a key factor in dry eye disease (DED) pathogenesis.
• Hyperosmotic stress induces endoplasmic reticulum (ER) stress in corneal epithelial cells, leading to inflammation and apoptosis.
• The unfolded protein response (UPR) and pro-apoptotic pathways are activated under hyperosmotic conditions.

Purpose of the Study:

• To investigate the protective effects of tauroursodeoxycholic acid (TUDCA) against hyperosmotic stress in corneal epithelial cells.
• To determine TUDCA's impact on ER stress markers and inflammatory mediators in DED models.

Main Methods:

• Human corneal epithelial cells and a human model of corneal epithelial differentiation were exposed to hyperosmotic conditions.
• Gene expression analysis was performed to assess UPR activation and inflammatory mediator levels.
• Cell viability assays, including DNA fragmentation and caspase-3 activation, were used to evaluate apoptosis.

Main Results:

• Hyperosmotic conditions upregulated genes associated with UPR and the pro-apoptotic factor DDIT3 in DED patients and in vitro models.
• TUDCA treatment significantly reduced hyperosmotic-induced corneal epithelial cell death, DNA fragmentation, and caspase-3 activation.
• TUDCA suppressed the expression of inflammatory mediators CXCL8 and IL5.

Conclusions:

• Hyperosmotic stress induces ER stress and apoptosis in corneal epithelial cells, contributing to DED.
• TUDCA demonstrates cytoprotective effects against hyperosmotic stress by mitigating ER stress and inflammation.
• TUDCA is a potential therapeutic candidate for managing dry eye disease.