Pathogenic Role of EPAC1 Signaling in Retinopathy of Prematurity

摘要 角膜意外暴露于化学物质(例如碱烧伤)或在针对美国平民的恐怖袭击期间或 武装力量(例如硫磺芥末烧伤)通常会导致角膜新生血管，其特征是 新生血管从角膜缘侵入角膜。角膜新生血管是一种视觉- 可能导致脂肪沉积、水肿、持续性炎症和疤痕形成的威胁条件，导致 角膜透明度和视力的损害。目前，治疗角膜只有几种选择 新生血管和这些治疗方法都有很大的局限性。有很大的需要开发新的 防止化学威胁下角膜新生血管和视力丧失的策略和治疗。在这 行政补充申请，我们建议进行试验，以产生初步数据，以 确定Epac1是否也在化学损伤后的角膜新生血管中发挥作用。这项计划的可行性 建议的工作得到了父母奖研究进展产生的数据的有力支持，以及 根据我们的初步数据。基于这项工作的试点数据，未来我们将进一步评估和优化 ESI-09等新型EPAC抑制剂对兔角膜氮芥末模型的治疗作用 烧了吧。拟议的试点工作，以及这项工作之后的未来研究，预计将显著 促进开发治疗角膜新生血管和术后恢复视力的新对策 化学威胁。

ABSTRACT Corneal exposure to chemicals by accident (e.g. alkali burn) or during a terrorist attack against U.S. civilians or armed forces (e.g. sulfur mustard burn) often leads to corneal neovascularization that is characterized by the invasion of new blood vessels into the cornea from the limbus. Corneal neovascularization is a vision- threatening condition that may lead to lipid deposition, edema, persistent inflammation and scarring, resulting in impairment of corneal transparency and visual acuity. Currently, there are only a few options to treat corneal neovascularization and these treatments have significant limitations. There is a great need to develop new strategies and therapies to prevent corneal neovascularization and vision loss against chemical threats. In this application for Administrative Supplements, we propose to conduct experiments to generate preliminary data to determine if Epac1 also plays a role in corneal neovascularization after chemical injury. The feasibility of the work proposed is strongly supported by data generated from the research progress of the parental award and by our preliminary data. Based on pilot data from this work, in the future, we will further evaluate and optimize the therapeutic effects of ESI-09 and other novel Epac inhibitors in a rabbit model of corneal nitrogen mustard burn. The proposed pilot work, together with future studies following this work, is expected to significantly facilitate the development of novel countermeasures to treat corneal neovascularization and restore vision after chemical threats.