Decoding epithelial regeneration in the cornea: multi-omic analysis reveals cellular plasticity as central mechanism

Area of Science:

• Ophthalmology
• Regenerative Medicine
• Molecular Biology

Background:

• The cornea, essential for vision, is prone to injury, making its rapid regeneration critical for tissue homeostasis.
• Corneal abrasions, though common, can lead to complications, highlighting gaps in understanding healing mechanisms.
• The cornea's exposed nature necessitates research into its repair processes and associated structures like the tear film.

Purpose of the Study:

• To comprehensively analyze molecular responses to corneal injury using multi-omics.
• To investigate the role of the tear film and lacrimal gland in corneal wound healing.
• To identify key molecular pathways and RNA modifications involved in corneal regeneration.

Main Methods:

• Unilateral corneal abrasion mouse model.
• Integrated transcriptomics, proteomics, and epitranscriptomics.
• RNA sequencing of corneal and lacrimal tissues; mass spectrometry of tear proteome.

Main Results:

• Significant corneal transcriptome modulation, affecting JAK-STAT, Wnt, and TGF-β pathways.
• Tear film deficiency altered wound healing and bilateral responses.
• Identified bilateralization of molecular responses in cornea and tears, influenced by tear film presence.

Conclusions:

• Epithelial cellular plasticity and RNA modifications are key to rapid corneal wound closure.
• The lacrimal gland and tear film play a crucial, previously underappreciated role in bilateral tissue regeneration.
• Novel regulatory roles for RNA methylation and signaling pathways in epithelial healing were uncovered.