Retinoic Acid Receptor Alpha- and Beta-Mediated Signaling Regulates Conjunctival Epithelial Cell Keratinization

Area of Science:

• Ophthalmology
• Cell Biology
• Molecular Biology

Background:

• Ocular surface disorders can lead to conjunctival epithelial cell (CjEC) keratinization, a process implicated in severe visual impairment.
• Understanding the molecular mechanisms underlying CjEC keratinization is crucial for developing effective treatments.

Purpose of the Study:

• To elucidate the molecular mechanisms of keratinization in human CjECs.
• To investigate the role of the vitamin A pathway in CjEC keratinization.
• To evaluate the therapeutic potential of vitamin A pathway modulators.

Main Methods:

• Generation of keratinized CjEC sheets using a closed system culture.
• Comprehensive gene expression analysis and quantitative real-time PCR (qRT-PCR) for keratinization and vitamin A pathway markers.
• Investigation of all-trans retinoic acid (ATRA) and Am80 effects, including RARA/RARB knockdown studies.

Main Results:

• Closed system culture successfully induced CjEC keratinization, confirmed by increased marker expression.
• Significant alterations in vitamin A pathway genes were observed alongside keratinization.
• ATRA and Am80 suppressed CjEC keratinization, while RARA or RARB knockdown increased keratinization marker expression.

Conclusions:

• CjEC keratinization is mediated by retinoic acid receptor alpha/beta (RARA/RARB)-dependent pathways.
• Vitamin A metabolites, ATRA and Am80, modulate vitamin A pathway gene expression and suppress conjunctival keratinization.
• Targeting the vitamin A pathway offers a potential therapeutic strategy for ocular surface disorders involving keratinization.