Corneal vascularization is a visually devastating result of injury, inflammation, and infection. The long-term objective of this project is the elucidation of mechanisms and inhibition of vascularization in corneal wound healing. Background: Several matrix metalloproteinases (MMPs) have been shown by us and others to participate in extracellular matrix remodeling during corneal wound healing. In our lab angiostatin, a cleavage fragment of plasminogen which has recently been discovered and studied in the context of tumor angiogenesis, has been found in association with MMP activity in the wounded cornea. This is the first identification of the presence and probable anti-angiogenic role of angiostatin in non-tumor tissue. Hypotheses: Angiostatin is produced in the cornea during wound healing. MMPs, activated in corneal wound healing, may contribute to angiostatin production, which serves to inhibit corneal neovascularization.
Specific Aims : A. Identify sites of MMP-2, -7, -9, and -12 and angiostatin production during corneal wound healing. B. Characterize the size and activity of angiostatin in the cornea and determine whether MMP(s) contribute to angiostatin production during corneal wound healing. C. Determine the possible roles of angiostatin and MMPs in maintaining corneal avascularity during wound healing. Significance: Discovery of the mechanisms that maintain corneal avascularity may allow us to prevent blindness caused by corneal vascularization. The study of MMPs and angiostatin in the cornea may provide valuable information about their behavior and possible clinical significance in other tissue.
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