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.

内皮抑素衍生短肽在角膜移植中的应用 抽象的： 眼外伤被列为战斗人员第四大常见伤害，这表明眼外伤至关重要 评估和促进退伍军人眼部健康的重要性。角膜新生血管，或 角膜中新血管（血管生成）和新淋巴管（淋巴管生成）的生长， 通常是由感染或严重角膜损伤引起的，包括爆炸压力、碎片穿透或 长期暴露在干燥的环境中。预防角膜新生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。约40,000个角膜 美国每年都会进行移植手术，但新的血管会生长在原来的血管或血管中。 移植角膜显着降低治疗成功率。例如，角膜排斥率 引入无血管宿主的比例为 0-10%，而显着增加的比例为 25-50% 在严重血管化的宿主中。特定淋巴管标志物的发现有所改善 我们对淋巴管生成的理解。然而，没有有效的治疗方法来防止角膜血管生长 目前存在角膜移植后。 XVIII 胶原蛋白 (col18a1) 及其裂解产物（内皮抑素、neostatin-7 和内皮抑素衍生肽）具有 被确定为角膜血管生成和淋巴管生成的调节剂，因此也是角膜移植的调节剂 拒绝。内皮抑素与促血管生成的血管内皮生长因子 (VEGF) 竞争结合 酪氨酸激酶受体（VEGFR）是介导 VEGF 作用所必需的。 VEGFR-1和-2是两个 受体是角膜基质中血管生成和淋巴管生成的主要介质， 上皮。在我们的实验中，我们建议使用高风险小鼠角膜移植模型 胶原蛋白 XVIII 敲除、Lecre-VEGFR1lox 和 lecre-VEGFR2lox 小鼠作为内皮抑素衍生受体的受体 短肽和 VEGF 陷阱，以确定抑制角膜血和的最有效策略 淋巴管生长。在此过程中，我们希望找到有效调节角膜的成分 新生血管形成，以促进未来改善角膜移植的药物的开发 成功率。我们的研究将产生的影响不仅与退伍军人事务部的医疗保健有关 使命，促进退伍军人的眼部健康和预防失明，但也指出了方法 成功移植角膜以外的组织。