Ursolic acid ameliorates ocular surface dysfunction in dry eye via targeting EGFR/RAS/RAF/MAP2K1/MAPK1 pathway

Area of Science:

• Ophthalmology and Pharmacology
• Molecular Biology
• Biochemistry

Background:

• Dry eye (DE) is an inflammatory ocular surface disease.
• Inflammation is a central pathological factor in DE.
• Ursolic acid (UA) possesses known anti-inflammatory properties.

Purpose of the Study:

• To evaluate the therapeutic effects of UA on dry eye (DE).
• To elucidate the underlying molecular mechanisms of UA in treating DE.
• To assess UA's protective effects on ocular surface cells and in an animal model.

Main Methods:

• Established hyperosmotic stress and animal models for DE.
• Utilized phenol-red cotton tests and slit-lamp examinations for damage assessment.
• Employed database mining, PPI network analysis, molecular docking, and integrative omics analyses (scRNA-seq, RNA-seq).

Main Results:

• UA eye drops preserved ocular surface integrity and alleviated DE symptoms.
• Network pharmacology identified the EGFR/RAS/RAF/MAP2K1/MAPK1 pathway as a key target.
• scRNA-seq confirmed the localization of pathway proteins in the anterior ocular segment, particularly the cornea.

Conclusions:

• UA eye drops demonstrate significant therapeutic potential for dry eye.
• The EGFR/RAS/RAF/MAP2K1/MAPK1 pathway is crucial for UA's efficacy in DE.
• UA offers a promising treatment strategy for ocular surface disorders.