Advanced stages of Age-related Macular Degeneration (AMD) are characterized by retinal neurodegeneration and aberrant angiogenesis, and mitochondrial dysfunction contributes to the pathogenesis of AMD. In this study, we tested the hypothesis that Humanin G (HNG), a cytoprotective mitochondrial-derived peptide, positively regulates cell proliferation, cell death, and the protein levels of angiogenesis and neurodegeneration markers, in normal (control) and AMD RPE transmitochondrial cybrid cell lines. These normal and AMD RPE transmitochondrial cybrid cell lines had identical nuclei derived from mitochondria-deficient ARPE-19 cell line, but differed in mitochondrial DNA (mtDNA) content that was derived from clinically characterized AMD patients and normal (control) subjects. Cell lysates were extracted from untreated and HNG-treated AMD and normal (control) cybrid cell lines, and the Luminex XMAP multiplex assay was used to examine the protein levels of angiogenesis and neurodegeneration markers. Humanin G reduced Caspase-3/7-mediated apoptosis, improved cell proliferation, and normalized the protein levels of angiogenesis and neurodegeneration markers in AMD RPE cybrid cell lines, thereby suggesting Humanin G's positive regulatory role in AMD.

年龄相关性黄斑变性 (AMD) 的晚期阶段以视网膜神经变性和异常血管生成为特征，线粒体功能障碍是 AMD 的发病机制之一。在这项研究中，我们测试了这样的假设：Humanin G (HNG)，一种细胞保护性线粒体衍生肽，在正常和 AMD RPE 线粒体杂种细胞中正向调节细胞增殖、细胞死亡以及血管生成和神经变性标记物的蛋白水平。来自线粒体缺陷 ARPE-19 细胞的相同细胞核，但来自临床特征性 AMD 患者和正常（对照）受试者的线粒体 DNA (mtDNA) 含量不同。从未经处理和 HNG 处理的 AMD 和正常（对照）胞质杂种中提取细胞裂解物，并使用 Luminex XMAP 多重测定来测量血管生成和神经变性标记物的蛋白质水平。HNG 减少了 Caspase-3/7 介导的细胞凋亡，改善了细胞增殖，并使 AMD RPE cybrid 细胞中血管生成和神经变性标记物的蛋白水平正常化，从而表明其在 AMD 中的积极调节作用。