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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.

总结