Collagen XVIII in Corneal Neovascularization

描述(申请人提供)：背景：角膜新生血管是世界范围内致盲的主要原因。本研究的目的是确定XVIII胶原蛋白及其蛋白降解片段在角膜新生血管形成中的作用。我们实验室已经发现，基质金属蛋白酶-7能裂解角膜和重组胶原XVIII，产生一个28 kDa的片段，可能调节角膜伤口愈合过程中的角膜新生血管形成。 假设：角膜中激活的基质金属蛋白酶-7可能参与内皮抑素和内皮抑素跨区片段的产生，从而抑制角膜新生血管。 具体目标： A.测定内皮抑素和基质金属蛋白酶-7衍生的XVIII胶原蛋白水解物片段在体内和体外角膜中的分布。 B.鉴定内皮抑素和基质金属蛋白酶-7衍生的XVIII胶原蛋白水解物片段在体外血管内皮细胞增殖、迁移和管状形成中的作用。 C.研究内皮抑素和基质金属蛋白酶-7衍生的XVIII胶原蛋白降解片段在体内角膜新生血管形成中的作用。 意义：了解维持角膜无血管的机制可能使我们能够预防由角膜新生血管引起的失明。研究内皮抑素和基质金属蛋白酶-7在角膜新生血管形成和伤口愈合中的作用可能为临床提供有价值的信息。

DESCRIPTION (provided by applicant): Background: Corneal neovascularization is a major cause of blindness worldwide. The objective of our research is to identify the role of collagen XVIII and its proteolytic fragments in corneal neovascularization. Our laboratory has found that MMP-7 cleaves corneal and recombinant collagen XVIII to generate a 28 kDa fragment which may regulate corneal neovascularization during corneal wound healing. Hypothesis: Activated MMP-7 in cornea may contribute to the production of endostatin and endostatin-spanning fragments, which inhibit corneal neovascularization. Specific Aims: A. To determine the distribution of endostatin and MMP-7-derived proteolytic fragment of collagen XVIII in the cornea in vivo and in vitro. B. To characterize the function of endostatin and MMP-7-derived proteolytic fragment of collagen XVIII in vascular endothelial cell proliferation, migration, and tube formation in vitro. C. To characterize the role of endostatin and MMP-7-derived proteolytic fragment of collagen XVIII in corneal neovascularization in vivo. Significance: Understanding the mechanisms that maintain corneal avascularity may allow us to prevent blindness caused by corneal neovascularization. The study of endostatin and MMP-7 in the cornea may provide valuable information about their possible clinical significance in corneal neovascularization and wound healing.