Corneal myofibroblasts and fibrosis.

Area of Science:

• Ophthalmology
• Cell Biology
• Tissue Engineering

Background:

• Myofibroblasts (alpha-smooth muscle actin [SMA]+ cells) are key players in the cornea's response to injury, infection, and surgery.
• Excessive myofibroblast activity leads to corneal scarring and fibrosis due to disordered extracellular matrix (ECM) production.
• These cells originate from various progenitors, including corneal fibroblasts and bone marrow fibrocytes, in response to growth factors like TGFβ1, TGFβ2, and PDGF.

Purpose of the Study:

• To elucidate the diverse roles and characteristics of corneal myofibroblasts in ocular health and disease.
• To investigate the impact of basement membrane integrity (epithelial basement membrane [EBM] and Descemet's basement membrane [DBM]) on myofibroblast behavior.
• To highlight the functional heterogeneity of myofibroblasts derived from different progenitor cells.

Main Methods:

• Proteomic analysis to compare protein expression and functions of myofibroblasts from distinct origins.
• Investigation of the correlation between basement membrane defects and myofibroblast persistence in the corneal stroma.
• Review of known myofibroblast functions, including ECM production, tissue contraction, and immune modulation.

Main Results:

• Myofibroblasts derived from different progenitors exhibit significant differences in protein expression and functional capabilities, indicating they are not interchangeable.
• Impaired regeneration or absence of the EBM and/or DBM promotes the development and sustained presence of myofibroblasts within the corneal stroma.
• Corneal myofibroblasts possess multifaceted functions, including ECM deposition, tissue remodeling via matrix metalloproteinases, and immune response modulation through toll-like receptors.

Conclusions:

• Understanding the heterogeneity of corneal myofibroblasts is critical for developing targeted therapies for corneal scarring and fibrosis.
• Basement membrane integrity plays a crucial role in regulating myofibroblast activity and preventing pathological scarring.
• Myofibroblasts are essential for corneal wound healing and defense against pathogens, but their dysregulation contributes to vision-impairing conditions.