The molecular basis of danger signal perception by retinal pigment epithelium (RPE) cells in the pathogenesis of age-related macular degeneration

在这项研究中，在激活的巨噬细胞中的选择性凋亡诱导剂在抑制TNF-α的产生和新的HDAC抑制剂在抑制TNF-α诱导的RPE细胞纤维化中的详细作用进行了研究。表明TNF-α和HDAC抑制剂在阻断RPE细胞和巨噬细胞亚群之间的恶性炎症循环的形成中的协同作用。首次阐明了RPE细胞分泌的miRNA介导危险感知的新分子机制，发现分泌的miRNA可能以旁分泌方式促进RPE细胞的变性。补体激活的经典和新发现的调节因子，即，CFH、CD 46、CD 59、clusterin和CTRP 6被发现在TNF-α触发RPE细胞上的炎性刺激后产生。免疫组织学证实了这些调节剂在人前眼组织中表达的特征。

In this study, the detailed roles of the inducer of selective apoptosis in activated macrophages in inhibiting the production of TNF-alpha and of the new HDAC inhibitor in inhibiting the TNF-alpha-induced fibrosis of RPE cells were investigated. The synergy between TNF-alpha and the HDAC inhibitor in the blockade of the formation of the vicious inflammatory cycle between RPE cells and the subpopulation of macrophages was indicated. The new molecular mechanism in danger perception mediated by miRNA secreted from RPE cells was first clarified, and the secreted miRNA was found to possibly propagate the degeneration of RPE cells in a paracrine manner. The classical and newly discovered regulators of complement activation, i.e., CFH, CD46, CD59, clusterin, and CTRP6, were found to be produced upon TNF-alpha triggered inflammatory stimuli on RPE cells. The characteristic features of the expression of these regulators in human anterior eye tissues were confirmed immunohistologically.