PDGF-Stimulated Corneal Keratocyte Motility and Migration Patterns on Aligned Collagen Fibrils Are Inhibited by...

Area of Science:

• Ophthalmology
• Biomaterials Science
• Cell Biology

Background:

• Decorin is a proteoglycan that inhibits transforming growth factor β1 (TGF-β1) signaling, showing potential for treating corneal scarring and blindness.
• Decorin also interacts with platelet-derived growth factor (PDGF), influencing cell migration in wound healing, but its role in the corneal stroma's unique extracellular matrix (ECM) is unclear.

Purpose of the Study:

• To investigate the interaction between decorin and PDGF signaling within an in vitro model of the corneal stroma's aligned collagen ECM.
• To understand how decorin affects PDGF-BB-stimulated keratocyte behavior and wound healing in this specific microenvironment.

Main Methods:

• Developed an in vitro model using decorin-coated aligned collagen fibrils mimicking the corneal stroma ECM.
• Assessed keratocyte response to PDGF-BB on decorin-coated versus uncoated aligned collagen fibrils.
• Quantified cell alignment, motility, PDGF receptor β (PDGFRβ) phosphorylation, and wound closure rates.

Main Results:

• Decorin significantly inhibited PDGF-BB-stimulated keratocyte alignment, motility, and wound closure on aligned collagen fibrils.
• Cells on decorin-coated substrates showed random migration, reduced alignment with collagen fibrils, and slower wound healing.
• PDGF-BB-stimulated cells on decorin exhibited increased branching and reduced solidity, altering their morphology.

Conclusions:

• Decorin's interaction with PDGF-BB presents challenges for corneal wound healing, despite its anti-fibrotic properties against TGF-β1.
• Therapeutic strategies for corneal wound healing need to consider decorin's dual effects on different signaling pathways and the corneal ECM.
• Further research is needed to optimize decorin-based therapies for effective corneal repair.