Macrophage miR146B and Ocular Neovascularization

老年性黄斑变性（AMD）是老年人失明的主要原因

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.