Mitochondrion. 2023 Nov 27:S1567-7249(23)00090-9. doi: 10.1016/j.mito.2023.11.001. Online ahead of print.
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 and AMD RPE transmitochondrial cybrid cells that had identical nuclei derived from mitochondria-deficient ARPE-19 cells but differed in mitochondrial DNA (mtDNA) content derived from clinically characterized AMD patients and normal (control) subjects. Cell lysates were extracted from untreated and HNG-treated AMD and normal (control) cybrids, and the Luminex XMAP multiplex assay was used to measure the protein levels of angiogenesis and neurodegeneration markers. HNG reduced Caspase-3/7-mediated apoptosis, improved cell proliferation, and normalized the protein levels of angiogenesis and neurodegeneration markers in AMD RPE cybrid cells, thereby suggesting its positive regulatory role in AMD.