Macrophages Transdifferentiate Into Myofibroblasts During Ocular Surface Inflammation

Area of Science:

• Ophthalmology
• Immunology
• Cell Biology

Background:

• Ocular surface inflammation and injury can cause fibrosis and vision loss.
• Myofibroblasts drive fibrosis by producing extracellular matrix (ECM) and alpha-smooth muscle actin (ɑ-SMA).
• Macrophages are known to promote fibrosis, but their direct ECM remodeling capacity is unclear.

Purpose of the Study:

• To investigate if macrophages transdifferentiate into myofibroblast-like cells during ocular surface inflammation.
• To analyze the role of macrophages in corneal fibrosis and ECM remodeling.

Main Methods:

• Utilized a mouse model of corneal injury and fibrosis.
• Quantified F4/80+ɑ-SMA+ macrophages during wound healing and remodeling stages.
• Activated human and mouse macrophages in vitro with pro-fibrotic cytokines (IL-10, TGF-β1).
• Assessed macrophage phenotype, ECM/cytoskeletal protein expression, and collagen gel contraction.

Main Results:

• F4/80+ɑ-SMA+ macrophages increased during corneal wound healing and remodeling.
• Macrophage transition correlated with the shift from inflammatory to pro-fibrotic microenvironment.
• In vitro, activated macrophages adopted myofibroblast characteristics (spindle shape, ɑ-SMA, desmin, fibronectin, collagen III expression).
• ɑ-SMA+ macrophages demonstrated significant collagen gel contraction, functionally mimicking myofibroblasts.

Conclusions:

• Macrophages possess the capacity to transdifferentiate into myofibroblasts in the context of ocular surface inflammation.
• This macrophage transdifferentiation contributes to fibrosis and ECM remodeling in ocular injuries.
• Findings suggest a novel cellular mechanism in ocular surface fibrosis progression.