Abstract：
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.
摘要：
最近,线粒体功能障碍作为年龄相关性黄斑变性(AMD)发病机制和进展的一个致病因素而受到关注.线粒体损伤在代谢中起关键作用，破坏细胞内代谢途径的平衡，例如氧化磷酸化(OXPHOS)和糖酵解。在这项研究中,我们关注氧化型低密度脂蛋白(ox-LDL),在AMD患者的视网膜中积累的玻璃疣的主要成分，并研究了它是否可能是视网膜色素上皮（RPE）细胞代谢改变的致病因素。我们发现，长期暴露于ox-LDL诱导脂肪酸β-氧化（FAO）的变化，OXPHOS,和糖酵解活性，并增加RPE细胞中线粒体活性氧的产生。值得注意的是,对代谢改变的影响因ox-LDL治疗的浓度和持续时间而异.此外,我们通过强调ARPE-19细胞的屏障功能和FAO活性低于诱导多能干细胞来源的RPE细胞,解决了将ARPE-19细胞用于视网膜疾病研究的局限性.我们的发现可以帮助阐明AMD代谢改变的潜在机制。
