Macrophage miR146B and Ocular Neovascularization

视网膜相关性黄斑变性（AMD）是年龄超过20岁的人失明的主要原因。 在工业化国家，50岁。晚期AMD的视力丧失是由于 称为脉络膜新生血管形成（CNV）的病理性血管生成或由脉络膜新生血管的丧失引起的病理性血管生成。 地图状萎缩的视网膜色素上皮和上覆的感光神经元。 CNV往往是灾难性的，并且占老年人严重视力丧失的约80-90%。 AMD.巨噬细胞介导的炎症反应在CNV的发病机制中起重要作用 在AMD。老年性黄斑变性中衰老的巨噬细胞通过活化改变而表现出功能障碍 和极化。基因表达变化的调控机制 在巨噬细胞内的特征很差。microRNA以一种新的水平调节基因表达。 但具有细胞特异性，并通过mRNA降解和翻译来实现 镇压 我们建议检查哪些miRNA在衰老的巨噬细胞中发生了改变， 特定的基因目标，他们调节和评估的影响，修改这两个 巨噬细胞中的miRNA和基因对它们的命运、功能和调节CNV的能力的影响。这 可能特别有见地，因为它可能确认年龄是一个连续变量， 在内在水平上定量调节。我们希望能够识别新的miRNA、基因和 分子途径，可以治疗AMD，以防止视力丧失 在这种毁灭性的疾病中。

Age-related macular degeneration (AMD) is the leading cause of blindness in people over 50 years of age in the industrialized world. Vision loss in advanced AMD is either due to pathologic angiogenesis called choroidal neovascularization (CNV) or from loss of the retinal pigmented epithelium and overlying photoreceptor neurons in geographic atrophy. CNV tends to be catastrophic and accounts for about 80-90% of severe vision loss in AMD. Macrophage-mediated inflammation plays a critical role in the pathogenesis of CNV in AMD. The aging macrophage manifests its dysfunction in AMD by altered activation and polarization. The regulatory mechanisms that govern gene expression changes within macrophages are poorly characterized. MicroRNAs regulate gene expression at a global level but with cellular specificity and do so by mRNA degradation and translational repression. We propose to examine which miRNAs are altered in the aging macrophage, identify the specific gene targets that they regulate and assess the effects of modifying both the miRNA and genes in macrophages on their fate, function and ability to regulate CNV. This could be especially insightful as it might confirm age as a continuous variable that can be quantitatively regulated at an intrinsic level. We hope to identify novel miRNA, genes and molecular pathways that could be therapeutically targeted in AMD to prevent vision loss in this devastating disease.