Oxidized-LDL Induces Metabolic Dysfunction in Retinal Pigment Epithelial Cells

DOI Web Site 参考文献35件 オープンアクセス
  • Tomomatsu Manami
    Department of Molecular Pathobiology, Faculty of Pharmaceutical Sciences, Kyushu University
  • Imamura Naoto
    Department of Molecular Pathobiology, Faculty of Pharmaceutical Sciences, Kyushu University
  • Izumi Hoshimi
    Department of Molecular Pathobiology, Faculty of Pharmaceutical Sciences, Kyushu University
  • Watanabe Masatsugu
    Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Division of Cardiovascular Medicine, Research Institute of Angiocardiology, Faculty of Medical Sciences, Kyushu University Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University
  • Ikeda Masataka
    Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Division of Cardiovascular Medicine, Research Institute of Angiocardiology, Faculty of Medical Sciences, Kyushu University
  • Ide Tomomi
    Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University Division of Cardiovascular Medicine, Research Institute of Angiocardiology, Faculty of Medical Sciences, Kyushu University
  • Uchinomiya Shohei
    Department of Medicinal Chemistry and Chemical Biology, Faculty of Pharmaceutical Sciences, Kyushu University
  • Ojida Akio
    Department of Medicinal Chemistry and Chemical Biology, Faculty of Pharmaceutical Sciences, Kyushu University
  • Jutanom Mirinthorn
    Department of Molecular Pathobiology, Faculty of Pharmaceutical Sciences, Kyushu University
  • Morimoto Kazushi
    Department of Molecular Pathobiology, Faculty of Pharmaceutical Sciences, Kyushu University
  • Yamada Ken-ichi
    Department of Molecular Pathobiology, Faculty of Pharmaceutical Sciences, Kyushu University

説明

<p>Recently, mitochondrial dysfunction has gained attention as a causative factor in the pathogenesis and progression of age-related macular degeneration (AMD). Mitochondrial damage plays a key role in metabolism and disrupts the balance of intracellular metabolic pathways, such as oxidative phosphorylation (OXPHOS) and glycolysis. In this study, we focused on oxidized low-density lipoprotein (ox-LDL), a major constituent of drusen that accumulates in the retina of patients with AMD, and investigated whether it could be a causative factor for metabolic alterations in retinal pigment epithelial (RPE) cells. We found that prolonged exposure to ox-LDL induced changes in fatty acid β-oxidation (FAO), OXPHOS, and glycolytic activity and increased the mitochondrial reactive oxygen species production in RPE cells. Notably, the effects on metabolic alterations varied with the concentration and duration of ox-LDL treatment. In addition, we addressed the limitations of using ARPE-19 cells for retinal disease research by highlighting their lower barrier function and FAO activity compared to those of induced pluripotent stem cell-derived RPE cells. Our findings can aid in the elucidation of mechanisms underlying the metabolic alterations in AMD.</p>

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