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Pathogenic Role of EPAC1 Signaling in Retinopathy of Prematurity

EPAC1 信号传导在早产儿视网膜病变中的致病作用

基本信息

批准号：
10087936
负责人：
Wenbo Zhang
金额：
$ 37.59万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-01 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10087936
关键词：
Address Astrocytes Blindness Blood Vessels Childhood Clinic Cold Therapy Cyclic AMP Data Development Disease Endothelial Cells Endothelium Genetic Human Impairment Integrins Ischemia Knockout Mice Mediator of activation protein Modeling Morphology Mus Neuronal Dysfunction Neuronal Injury Neurons Oxygen Pathogenicity Pathologic Pathologic Neovascularization Pathway interactions Patients Pharmacology Phosphorylation Physiological Play Process Property Protein Isoforms Proteins Research Retina Retinal Diseases Retinal Ganglion Cells Retinal Neovascularization Retinopathy of Prematurity Role Second Messenger Systems Signal Transduction Testing Therapeutic Effect Thick Vascular Diseases Visual impairment base calmodulin-dependent protein kinase II design improved inhibitor/antagonist laser photocoagulation neovascular neovascularization neuron apoptosis neuron loss neurovascular novel novel strategies preservation prevent repaired retina blood vessel structure retinal ischemia retinal neuron standard care standard of care time use

项目摘要

Project title: Pathogenic Role of EPAC1 Signaling in Retinopathy of Prematurity SUMMARY Retinopathy of prematurity (ROP) is the leading cause of vision impair and blindness in the USA in the childhood. Laser photocoagulation is the standard-of-care for treating retinal neovascularization (NV) in ROP, and supplement cryotherapy is occasionally used in severe cases. These treatments only target pathological neovascularization (NV) and have many limitations. There is great need for new strategies and therapies to target other aspects of the disease, including retinal neuronal injury, and promote vascular repair in addition to the control of NV. This study is to determine the role of Epac1 in neuronal injury, pathological NV and physiological vascular repair, and determine the therapeutic effect of Epac inhibitors. Our central hypothesis is that Epac1 activation plays a key causal role in retinal neuronal injury, impairing vascular repair and promoting retinal pathological neovascularization during oxygen-induced retinopathy. This application will, for the first time, use Epac1 global KO mice, Epac1 conditional KO mice and novel Epac inhibitor to investigate the cAMP/Epac1 pathway in retinal neuronal injury, NV and vascular repair. It will address specific contributions of neuronal vs. endothelial Epac1 in these processes, and investigate potential mechanisms of Epac1-induced retinal neuronal and vascular alternations. The research is expected to significantly advance the mechanistic understanding of retinal neurovascular pathologic changes and should facilitate the development of novel strategies to prevent NV, protect retinal neurons and improves vascular repair in ROP.

项目名称：EPAC1信号在早产儿视网膜病变中的致病作用