REGULATION OF VESSEL REGRESSION IN ISCHEMIC RETINOPATHY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 早产儿视网膜病变(ROP)是一种病理性视网膜新生血管障碍，可导致终生失明。该项目的长期目标是更好地了解视网膜新生血管的机制，以便开发抗血管生成的治疗方法。我们推测，直接调节视网膜前内皮细胞(EC)的凋亡将是一种有效的抗血管生成方法，尽管有多种因素可以促进病理性血管生成。作为一类新的信号分子，EPhin/Eph受体也是调控EC新生血管和细胞凋亡的候选分子。为了验证我们的假说并确定导致血管簇凋亡的机制，我们提出了以下具体目标：1)确定可导致血管内皮细胞凋亡和促进血管簇退化的特定死亡受体，特别是确定直接激活Fas是否会诱导血管退行性变；2)利用转基因小鼠，确定小胶质细胞和巨噬细胞在视网膜新生血管退行性变中的作用及其诱导细胞凋亡的能力；3)通过开发新的治疗方法来诱导血管退行性变，进一步了解eSpein/Eph受体在视网膜新生血管形成中的作用，使用可溶性配体来调节OIR小鼠模型中的eSpein/Eph受体。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Retinopathy of prematurity (ROP) is a disorder of pathological retinal neovascularization, which can result in life-long blindness. The long-term goal of this project is to acquire a better understanding of the mechanisms surrounding retinal neovascularization in order to develop anti-angiogenesis therapies. We hypothesize that directly modulating pre-retinal endothelial cell (EC) apoptosis will be an efficient anti-angiogenic approach despite the multiple factors that can promote pathological angiogenesis. A novel class of signaling molecules, the ephrin/Eph receptors are also candidate molecules to regulate EC neovascularization and apoptosis. In order to test our hypothesis and identify mechanisms that are responsible for vascular tuft apoptosis, we propose the following specific Aims: 1) Identify specific death receptors that lead to EC apoptosis and promote tuft regression, specifically determine if direct activation of Fas will induce vessel regression; 2) Identify the contribution of microglia and macrophages to the regression of retinal neovascularization and their ability to induce apoptosis through the use of genetically altered mice; and 3) Further understand the role of ephrin/Eph receptors in retinal neovascularization by developing new therapeutic approaches to induce vessel regression, using soluble ligands to modulate the ephrin/Eph receptors in the mouse model of OIR.