Matrix Metalloproteinase 14 in Corneal Neovascularization

Corneal neovascularization (CoNV) disrupts the natural avascularity of the cornea, leading to loss of transparency and visual impairment. Among matrix metalloproteinases (MMP), MMP-14, a membrane-bound MMP, plays a central role in CoNV through matrix remodeling, activation of pro-MMP-2, modulation of growth factors-induced signaling, and regulation of vascular endothelial cell behavior. Under pathogenic conditions, MMP-14 promotes angiogenesis by degrading stromal collagen, enhancing vascular endothelial growth factor (VEGF) signaling, and stimulating vascular endothelial cell migration. However, MMP-14 can also exert anti-angiogenic effects by generating endostatin-like fragments such as neostatin-14. MMP-14 also participates in corneal wound healing and lymphangiogenesis, making it a promising therapeutic target for CoNV. Standard therapies for CoNV, such as corticosteroids, immunosuppressants, and anti-VEGF agents, remain partially effective. Novel strategies targeting MMP-14, including small-molecule inhibitors, selective use of TIMP-2, and recombinant antibodies, are being explored. A deeper understanding of how membrane-bound MMP-14 is regulated and functions in different contexts may allow better modulation of angiogenesis, ultimately preserving corneal clarity and visual function after injury or inflammation.