TGFβ and PDGF-B signaling blockade inhibits myofibroblast development from both bone marrow-derived and keratocyte-derived precursor cells in vivo

Area of Science:

• Ophthalmology
• Cell Biology
• Regenerative Medicine

Background:

• Corneal stromal haze, a form of opacity, is primarily associated with myofibroblasts.
• Myofibroblasts contributing to corneal haze can originate from both local corneal cells and bone marrow-derived precursors.
• Understanding the regulation of these myofibroblasts is crucial for developing treatments for corneal opacity.

Purpose of the Study:

• To investigate the role of transforming growth factor beta (TGFβ) and platelet-derived growth factor (PDGF) in the development of bone marrow-derived myofibroblasts contributing to corneal haze.
• To determine if blocking TGFβ or PDGF signaling affects myofibroblast populations derived from both bone marrow and corneal sources.

Main Methods:

• Utilized a green fluorescent protein (GFP) chimeric bone marrow mouse model to track cell origins.
• Employed plasmid vectors designed to block TGFβ or PDGF signaling pathways.
• Administered treatments post-phototherapeutic keratectomy and assessed alpha-smooth muscle actin (α-SMA)-positive cells at the peak of corneal haze.

Main Results:

• Treatment with TGFβ or PDGF blocking vectors significantly reduced the number of α-SMA-positive myofibroblasts compared to control groups.
• Both bone marrow-derived (GFP+) and keratocyte/corneal fibroblast-derived (GFP-) myofibroblasts were diminished by the blocking vectors.
• Myofibroblasts were found to be composed of 30-60% bone marrow-derived cells and 40-70% keratocyte-derived cells in individual animals.

Conclusions:

• TGFβ and PDGF signaling are critical regulators of corneal myofibroblast development.
• Targeting TGFβ and PDGF pathways holds therapeutic potential for reducing corneal haze by inhibiting myofibroblast proliferation from both local and systemic sources.