Expression of MMP, HPSE, and FAP in stroma promoted corneal neovascularization induced by different etiological...

Area of Science:

• Ophthalmology
• Cell Biology
• Biochemistry

Background:

• Corneal neovascularization (CNV) is a pathological process involving new blood vessel growth into the cornea.
• Understanding the molecular mechanisms driving CNV is crucial for developing effective treatments.
• Matrix metalloproteinases (MMPs), heparanase (HPSE), and fibroblast activation protein (FAP) are implicated in tissue remodeling and angiogenesis.

Purpose of the Study:

• To investigate the relationship between MMP-2, MMP-9, HPSE, and FAP expression in the corneal stroma and CNV.
• To compare these molecular markers in CNV models induced by various etiological factors.

Main Methods:

• Established five distinct CNV models: alkaline burn, fungal infection, suturing, immunogen implantation, and tumor cell implantation.
• Assessed CNV morphology and timing via slit lamp examination.
• Analyzed stromal inflammation and neovascularization using histopathology.
• Detected MMP-2, MMP-9, HPSE, and FAP expression through immunohistochemistry and double immunofluorescence staining.

Main Results:

• CNV onset occurred by day three across all models, with distinct morphologies observed (dendritic, brush, triangle).
• Inflammatory cells and neovascular vessels appeared concurrently in the stroma from day three to day 14.
• MMP-2, MMP-9, and HPSE expression preceded neovascularization, appearing on day one and persisting throughout the observation period.
• FAP-positive cells were predominantly located around CD31-positive vascular endothelial cells.

Conclusions:

• Corneal neovascularization exhibits varied morphologies depending on the inducing etiological factor.
• Stromal inflammation and the expression of MMPs, HPSE, and FAP appear to act as early indicators or 'pioneers' for CNV development.