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VEGFR2 Modulates Corneal Angiogenesis and Lymphangiogenesis

VEGFR2 调节角膜血管生成和淋巴管生成

基本信息

批准号：
8569510
负责人：
JIN-HONG CHANG
金额：
$ 23.93万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8569510
关键词：
Alkalies Binding Blindness Blood Vessels Breeding Burn injury Cell Proliferation Cells Clinical Cornea Corneal Injury Corneal Neovascularization Disease Endothelial Cells Epithelial Equilibrium Experimental Models Eye Goals Green Fluorescent Proteins Image In Vitro Individual Infection Knock-out Knockout Mice Lead Ligands Limbus Corneae Lymphangiogenesis Lymphatic Lymphatic vessel Maintenance Mediating Membrane Methods Modeling Molecular Mus Neoplasm Metastasis Play Procedures Process Production Protein Isoforms Regulation Relative (related person)Research Role Signal Transduction Therapeutic Time Transplantation Tube 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 angiogenesis cadherin 5 cell motility design dimer in vivo injured limbal migration neovascularization novel therapeutic intervention prevent public health relevance receptor receptor binding research study response spatiotemporal tumor growth

项目摘要

DESCRIPTION (provided by applicant): Corneal neovascularization (NV) is a common, disabling condition and a major cause of blindness that can follow corneal injury or infection. Our long term goal is to characterize the role of VEGF receptors in the two central corneal vascularization processes, vascular angiogenesis (VA) and lymphangiogenesis (LA). The involvement of the epithelial, soluble form of VEGFR-2 (sVEGFR-2) in LA has been well characterized. However, the role of membrane- bound, vascular VEGFR-2 (mbVEGFR-2) in corneal VA and LA has not. These proposed experiments are designed to characterize the potential angiogenic and lymphangiogenic roles of the membrane bound isoform of VEGFR-2. We propose the hypothesis that vascular mbVEGFR2 may have distinct roles, separate from those of VEGFR1 or VEGFR3, in response to induction by VEGF-A (towards VA) or VEGF-C (towards LA) in corneal angiogenesis/ lymphangiogenesis. Two specific aims have been proposed to characterize the role of VEGFR- 2 in corneal angiogenesis and lymphangiogenesis. Aim A. Use inducible, conditional knockout mouse lines to determine whether mbVEGFR2 maintains a counterbalanced relationship with sVEGFR1 and sVEGFR2 in the cornea. Aim B. Characterize the individual roles of pro- angiogenic agents on VEGFR activity and VA/LA initiation, progression, and maintenance. SIGNIFICANCE: The endothelial receptor mbVEGFR2 sits at the crossroads of VA/LA initiation. Our proposed research strategy will define the role mbVEGFR2 plays in maintaining the vascular/avascular balance at the corneal border in both the normal and injured eye, increase our understanding of the VEGFR2-R3 relationship, and separate the relative contributions of pro-angiogenic agents and mbVEGFR2 to proliferation, migration, and tube formation. A better understanding of the role this receptor plays in both the normal and injured eye is of clinical importance because it increases our ability to develop therapeutic methods to prevent or reverse pathological VA and LA in the cornea, in other transplant procedures, and in tumor growth and metastasis.

描述（由申请人提供）：角膜新生血管（NV）是一种常见的致残性疾病，也是角膜损伤或感染后致盲的主要原因。我们的长期目标是表征VEGF受体在两个中央角膜血管化过程中的作用，即血管生成（VA）和淋巴管生成（LA）。上皮可溶性形式的VEGFR-2（sVEGFR-2）在LA中的参与已被充分表征。然而，膜结合的血管VEGFR-2（mbVEGFR-2）在角膜VA和LA中的作用还没有。这些拟定实验旨在表征膜结合VEGFR-2亚型的潜在血管生成和淋巴管生成作用。我们提出的假设，血管mbVEGFR2可能有不同的作用，从VEGFR1或VEGFR3，在响应诱导VEGF-A（对VA）或VEGF-C（对LA）在角膜血管生成/淋巴管生成。已经提出了两个具体的目标来表征VEGFR-2在角膜血管生成和淋巴管生成中的作用。目标A。使用诱导型、条件性基因敲除小鼠系来确定mbVEGFR2是否与角膜中的sVEGFR1和sVEGFR2保持平衡关系。瞄准B。表征促血管生成药物对VEGFR活性和VA/LA启动、进展和维持的个体作用。意义：内皮受体mbVEGFR2位于VA/LA起始的十字路口。我们提出的研究策略将确定mbVEGFR2在维持正常和受伤眼睛角膜边缘血管/无血管平衡中的作用，增加我们对VEGFR2-R3关系的理解，并分离促血管生成剂和mbVEGFR2对增殖，迁移和管形成的相对贡献。更好地了解这种受体在正常和受伤的眼睛中所起的作用具有临床重要性，因为它增加了我们开发治疗方法的能力，以预防或逆转角膜中、其他移植手术中以及肿瘤生长和转移中的病理性VA和LA。