Endostatin-derived Short Peptides in Corneal Transplantation

内皮抑素衍生的短肽在角膜移植中的应用

• 批准号: 8627925
• 负责人: JIN-HONG CHANG
• 金额: --
• 依托单位: JESSE BROWN VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8627925
• 关键词: Affect; Affinity; Alanine; Animal Model; Binding; Biological Assay; Biological Models; Blindness; Blood; Blood Vessels; CD8B1 gene; Cell Proliferation; Cells; Clinical; Collagen; Collagen Type XVIII; Cornea; Corneal Injury; Corneal Neovascularization; Corneal Stroma; Disease; Endostatins; Endothelial Cells; Environment; Epithelial; Exhibits; Explosion; Exposure to; Eye Injuries; Future; Graft Rejection; Growth; Health; Healthcare; Human Resources; Immunoprecipitation; In Vitro; Incidence; Infection; Injury; Invaded; Keratoplasty; Knock-out; Knockout Mice; Ligands; Lymphangiogenesis; Lymphatic Endothelial Cells; Lymphatic vessel; Mediating; Mediator of activation protein; Membrane; Messenger RNA; Methods; Mission; Modeling; Molecular; Mus; Mustard Gas; Operative Surgical Procedures; Penetration; Peptides; Pharmaceutical Preparations; Physiological; Prevalence; Production; Proteins; Receptor Protein-Tyrosine Kinases; Recovery; Research; Role; Scanning; Solutions; Specificity; Surface Plasmon Resonance; Testing; Time; Tissue Donors; Tissue Transplantation; Tissues; Transplantation; Trauma; United States; Ursidae Family; VEGF Trap; Vascular Endothelial Cell; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor Receptor; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factor Receptor-3; Vascular Endothelial Growth Factors; Vascularization; Veterans; Work; abstracting; angiogenesis; cell motility; combat; common treatment; corneal epithelium; drug development; effective therapy; experience; high risk; improved; macrophage; neovascularization; new growth; pressure; prevent; public health relevance; receptor; receptor binding; research study; response; success

Endostatin-derived short peptide in corneal transplantation Abstract: Ocular trauma's ranking as the fourth most common injury among combat personnel indicates the vital importance of evaluating and promoting ocular health among veterans. Corneal neovascularization, or the growth of new blood vessels (angiogenesis) and new lymphatic vessels (lymphangiogenesis) in the cornea, often results from infection or severe corneal injury including explosion pressure, penetration by debris, or long-term exposure to dry environments. Preventing corneal neovascularization generally necessitates in high risk corneal transplantation in order to restore eyesight and prevent blindness. Approximately 40,000 corneal transplants are performed in the United States annually, but new blood vessel growth in either the original or transplanted cornea significantly diminishes treatment success rates. For example, the rate of rejected corneas that are introduced into avascular hosts is 0-10%, compared to the significantly increased rate of 25-50% among hosts that are severely vascularized. The discovery of specific lymphatic vessel markers has improved our understanding of lymphangiogenesis. However, no effective treatment to prevent corneal vessel growth after corneal transplantation currently exists. Collagen XVIII (col18a1) and its cleavage products (endostatin, neostatin-7 and endostatin-derived peptides) have been identified as modulators of corneal angiogenesis and lymphangiogenesis and therefore of corneal transplant rejection. Endostatin competes with pro-angiogenic Vascular Endothelial Growth Factors (VEGFs) for binding to the tyrosine-kinase receptors, VEGFRs, that are necessary to mediate the effects of VEGFs. VEGFR-1 and -2 are two receptors that are primary mediators of angiogenesis and lymphangiogenesis in the corneal stroma and epithelium. In our experiment, we propose to use high-risk mouse corneal transplantation models with collagen XVIII knockout, Lecre-VEGFR1lox and lecre-VEGFR2lox mouse as recipients with endostatin-derived short peptide and VEGF traps, to determine the most effective strategies for inhibiting corneal blood and lymphatic vessel growth. In so doing, we hope to identify components that effectively modulate corneal neovascularization in order to facilitate the future development of drugs that will improve corneal transplant success rates. Our research will bear implications that are not only pertinent to the Veteran Affairs healthcare mission, promoting ocular health and preventing blindness among veterans, but also indicate methods for successful transplantation of tissues other than just the cornea.

角膜移植中的内接抑制素的短肽 抽象的： 眼部创伤的排名是战斗人员中第四大伤害，表明至关重要 评估和促进退伍军人眼部健康的重要性。角膜新血管形成，或 新血管（血管生成）和角膜中新的淋巴管（淋巴管生成）的生长， 通常是由于感染或严重的角膜损伤引起的，包括爆炸压力，碎屑穿透或 长期暴露于干燥环境。防止角膜新血管形成通常需要高 冒着角膜移植的风险，以恢复视力并防止失明。大约40,000个角膜 每年在美国进行移植，但原始血管的生长或 移植的角膜大大降低了治疗成功率。例如，被拒绝的角膜速率 引入无血管宿主的时间为0-10％，而显着增加了25-50％ 在严重血管化的宿主中。特定淋巴管标记的发现有所改善 我们对淋巴管生成的理解。但是，没有有效的治疗方法来防止角膜血管生长 角膜移植后目前存在。 胶原蛋白XVIII（COL18A1）及其裂解产物（内胞霉素，Neostatin-7和内抑素衍生的肽）具有 被鉴定为角膜血管生成和淋巴管生成的调节剂，因此是角膜移植的 拒绝。内抑素与亲血管生成的血管内皮生长因子（VEGF）竞争，以与 酪氨酸激酶受体，VEGFR，是介导VEGFS的作用所必需的。 VEGFR -1和-2是两个 是角膜基质和淋巴管生成的主要介体的受体 上皮。在我们的实验中，我们建议使用高风险的小鼠角膜移植模型 胶原蛋白XVIII淘汰，lecre-vegfr1lox和lecre-vegfr2lox鼠标作为源自内抑素的受体 短肽和VEGF陷阱，以确定抑制角膜血液和的最有效策略 淋巴管生长。这样做，我们希望确定有效调节角膜的组件 新血管化以促进将来可以改善角膜移植的药物的发展 成功率。我们的研究将具有与资深事务医疗保健相关的影响 任务，促进眼健康并防止退伍军人失明，但也指出 除了角膜以外，成功移植了组织。