Telomerase in choroidal neovascularization

端粒酶在脉络膜新生血管中的作用

基本信息

批准号：
9808042
负责人：
Nagaraj Kerur
金额：
$ 24.23万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9808042
关键词：
Age related macular degeneration Angiogenesis Inhibitors Biology Blindness Blood Blood Vessels Bone Marrow Cells Choroidal Neovascularization Complex Corneal Neovascularization DNA biosynthesis Data Development Diabetic Retinopathy Disease Endothelial Cells Endothelium Equilibrium Experimental Models Exudative age-related macular degeneration Eye Eye diseases Genes Genetic Genetic Transcription Growth Homeostasis Human Hyperactive behavior Hypoxia Impairment Knowledge Laboratories Laser injury Lasers Measures Mediating Mediator of activation protein Messenger RNA Modeling Molecular Mus Neovascular Glaucoma Pathologic Patients Pharmaceutical Preparations Pharmacology Phenotype Proliferating RNA-Directed DNA Polymerase Reporting Research Retina Retinal Retinal Vein Occlusion Retinopathy of Prematurity Ribonucleoproteins Risk Role Signal Transduction Telomerase Telomerase RNA Component Telomerase inhibition Testing Tissues Transcriptional Activation Untranslated RNA Vascular Diseases Vascular Endothelial Growth Factors Vision angiogenesis anticancer research bevacizumab effective therapy experience insight macrophage mouse model neovascularization novel therapeutics ocular angiogenesis proliferative diabetic retinopathy response senescence synergism tumor

项目摘要

SUMMARY Aberrant ocular angiogenesis underlies catastrophic loss vision due to multiple conditions including neovascular age-related macular degeneration (nvAMD), proliferative diabetic retinopathy (DR), retinopathy of prematurity (ROP), and ischemic retinal vein occlusion. Although anti-VEGF therapy has revolutionized the management of such disorders, the drugs suffer from several roadblocks. Prolonged anti-VEGF therapies are accompanied by serious risks and significant number of patients still experience vision loss despite treatment. Therefore, new insights into molecular mechanisms that promote angiogenesis in the retina are needed for the development of more effective therapies. Recent studies in the laboratory have identified a proangiogenic activity of telomerase in mouse model of experimental choroid neovascularization (CNV). Studies proposed here will build on these exciting new findings to test the hypothesis that telomerase is an important mediator of aberrant ocular angiogenesis. To this end, employing mouse model of laser injury-induced choroidal neovascularization, we will rigorously define proangiogenic activity of telomerase and examine whether and how the proangiogenic mechanisms of telomerase and VEGF signaling converge and interface. Overall, we anticipate that this study will not only provide new insights into the role of telomerase in ocular angiogenesis, but also usher in new avenues of research for examining the synergy between telomerase biology ocular angiogenesis and retinal vasculopathies in the context multiple blinding diseases.

概括异常的眼部血管生成是多种情况导致灾难性视力丧失的基础包括新生血管性年龄相关性黄斑变性（nvAMD）、增殖性糖尿病视网膜病变（DR）、早产儿视网膜病变（ROP）和缺血性视网膜静脉阻塞。虽然抗 VEGF 疗法彻底改变了此类疾病的治疗方法，该药物患有以下问题：几个障碍。长期抗 VEGF 治疗伴随着严重的风险尽管接受治疗，仍有相当多的患者出现视力丧失。因此，新需要深入了解促进视网膜血管生成的分子机制开发更有效的疗法。实验室最近的研究发现小鼠实验性脉络膜新生血管模型中端粒酶的促血管生成活性（CNV）。这里提出的研究将建立在这些令人兴奋的新发现的基础上来检验以下假设：端粒酶是异常眼部血管生成的重要介质。为此，采用激光损伤诱导脉络膜新生血管的小鼠模型，我们将严格定义端粒酶的促血管生成活性，并检查是否以及如何促血管生成端粒酶和 VEGF 信号传导汇聚和相互作用的机制。总体而言，我们预计这项研究不仅将为端粒酶在眼部血管生成中的作用提供新的见解，而且还开辟了新的研究途径来检查端粒酶生物学之间的协同作用多种致盲疾病背景下的眼部血管生成和视网膜血管病变。