Expression of MMP, HPSE, and FAP in Stroma Promoted Corneal Neovascularization Induced by Different Etiological Factors

PURPOSE: To observe the relationship between the expression of matrix metalloproteinases (MMP-2, MMP-9), heparanase (HPSE), and fibroblast activation protein (FAP) in stroma and corneal neovascularization induced by different etiological factors. METHODS: Five models were established: alkaline burn, fungal infection, suturing, immunogen implantation, and tumor cell implantation. The ingrowth time and morphology of corneal neovascularization in each model was observed by slit lamp. Inflammation and neovascularization in the corneal stroma were examined by histopathology. MMP-2, MMP-9, HPSE, and FAP were detected by immunohistochemistry or double immunofluorescence staining. RESULTS: The neovascular vessels started to invade the cornea from the third day in each model. The corneal neovascularization presented dendritic-form, brush-form, and triangle-form in alkaline burn, fungal infection, and suturing models, respectively, and reached to the central cornea in the latter two models. The inflammatory cells appeared in the stroma on the first day, while neovascular vessels grew into the stroma from the third day and both of them accompanied each other from 3-14 days in each model. MMP-2, MMP-9, and HPSE appeared before the neovascularization on the first day and accompanied it from 3-14 days in each model. FAP(+) cells occurred mainly around CD31(+) vascular endothelial cells in each model. CONCLUSION: The corneal neovascularization induced by different etiological factors have different morphologies. The inflammation and the expression of MMP, HPSE, and FAP in stroma may serve as pioneers for the growth of corneal neovascularization.