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== Endostatin is a polypeptide of 184 amino acids, corresponding to the globular domain found at the C-terminal of type XVIII collagen, and it is the most studied of the endogenous angiogenesis inhibitors.
Endostatin, a putative antiangiogenic factor, is a 20-kDa proteolytic fragment of collagen XVIII.29 Recombinant endostatin and its related fragments have been shown to inhibit bFGF-induced corneal NV in vivo and bFGF- and VEGF-induced vascular endothelial cell migration and proliferation in vitro.30 Specifically, endostatin implanted in the cornea demonstrated an inhibition of the bFGF-induced NV. Collagen XVIII is a nonfibrillar collagen localized mainly to the corneal vascular and epithelial basement membrane. Cleavage of collagen XVIII by proteases (including MMPs, cathepsin L, and elastase) generates endostatin-like fragments that may display antiangiogenic properties. Local production of endostatin may occur during corneal wound healing, as both the cleaving enzymes (MMPs) and the substrate (collagen XVIII) are present in the basement membrane area to prevent corneal NV. Endostatin has been approved by the US Food and Drug Administration (FDA) for the treatment of NV-related cancer; thus, it may be an additional drug that can be added to anti-VEGF therapy to treat corneal NV- and lymphangiogenesis-related disorders. ==
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