Collagen XVIII in Corneal Neovascularization

描述（由申请人提供）：背景：角膜新生血管是全球范围内致盲的主要原因。本研究的目的是确定胶原XVIII及其蛋白水解片段在角膜新生血管形成中的作用。我们的实验室已经发现MMP-7切割角膜和重组胶原XVIII以产生28 kDa片段，其可以在角膜伤口愈合期间调节角膜新生血管形成。 假设：角膜中激活的MMP-7可能有助于内皮抑素和内皮抑素跨片段的产生，从而抑制角膜新生血管。 具体目标： A.目的：研究内皮抑素和MMP-7衍生的胶原蛋白XVIII在角膜中的分布。 B。研究内皮抑素和MMP-7衍生的胶原蛋白XVIII蛋白水解片段在体外血管内皮细胞增殖、迁移和管腔形成中的作用。 C.目的探讨内皮抑素和基质金属蛋白酶7（MMP-7）衍生的XVIII型胶原蛋白水解片段在角膜新生血管形成中的作用。 意义：了解维持角膜无血管性的机制可能使我们能够预防角膜新生血管导致的失明。内皮抑素和MMP-7在角膜中的研究可能为它们在角膜新生血管和伤口愈合中可能的临床意义提供有价值的信息。

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.