Extracellular Vesicles Secreted by Corneal Epithelial Cells Promote Myofibroblast Differentiation

Area of Science:

• Ophthalmology
• Cell Biology
• Extracellular Vesicles Research

Background:

• The corneal epithelium is crucial for ocular surface injury response.
• Corneal epithelial cells secrete profibrotic factors and extracellular vesicles (EVs) upon wounding.
• Myofibroblast differentiation drives corneal scar formation.

Purpose of the Study:

• To investigate if corneal epithelial-derived EVs promote myofibroblast differentiation.
• To determine the effect of these EVs on corneal fibroblast phenotype, contractility, proliferation, and migration.
• To characterize the protein cargo within these EVs.

Main Methods:

• In vitro culture of corneal epithelial cells and fibroblasts.
• Treatment of corneal fibroblasts with epithelial cell-derived EVs.
• Analysis of myofibroblast differentiation markers (e.g., α-smooth muscle actin).
• Assessment of fibroblast contractility.
• Proteomic analysis of EV contents.

Main Results:

• EV treatment increased myofibroblast differentiation and α-smooth muscle actin expression.
• Corneal fibroblast contractility was elevated after EV treatment.
• Proteomic analysis identified fibronectin and thrombospondin-1 as dominant proteins within the EVs.
• Proteins regulating protein translation were also abundant in EVs.

Conclusions:

• Corneal epithelial-derived EVs play a novel role in promoting myofibroblast differentiation and contractility.
• EVs contain profibrotic proteins like fibronectin and thrombospondin-1, contributing to corneal scarring.
• These findings highlight EVs as potential therapeutic targets for preventing corneal scarring.