Pathogenic Role of EPAC1 Signaling in Retinopathy of Prematurity

项目名称：EPAC 1信号通路在早产儿视网膜病变中的致病作用 总结 早产儿视网膜病变（ROP）是美国视力损害和失明的主要原因， 童年.激光光凝是治疗ROP中视网膜新生血管（NV）的标准治疗方法， 在严重病例中偶尔使用补充冷冻疗法。这些治疗只针对病理性的 新生血管形成（NV），并且具有许多局限性。我们非常需要新的策略和疗法， 针对疾病的其他方面，包括视网膜神经元损伤，并促进血管修复， 控制NV。本研究旨在探讨Epac 1在神经元损伤、病理性NV及 生理性血管修复，并确定Epac抑制剂的治疗效果。我们的核心假设是 Epac 1激活在视网膜神经元损伤中起关键的因果作用，损害血管修复并促进血管再生。 氧诱导视网膜病变过程中视网膜病理性新生血管形成。该应用程序将首先 时间，使用Epac 1全基因敲除小鼠、Epac 1条件性敲除小鼠和新型Epac抑制剂研究Epac 1基因敲除小鼠的免疫功能。 cAMP/Epac 1通路在视网膜神经元损伤、NV和血管修复中的作用本报告将讨论以下方面的具体贡献： 神经元与内皮Epac 1在这些过程中，并探讨Epac 1诱导的潜在机制 视网膜神经元和血管改变。该研究有望显著推进 了解视网膜神经血管的病理变化，应有助于开发新的 预防NV、保护视网膜神经元和改善ROP中的血管修复的策略。

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.