Hyperglycemia (HG) affects cellular organelle including mitochondrion in retina that diminishes mitochondrial biogenesis by downregulation of nuclear transcription factors peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1α) and mitochondrial transcription factor A (TFAM). Mitochondrial dysfunction has been linked to diabetic retinopathy (DR). Carotenoids reported to modulate mitochondrial biogenesis in HG. Aim of the study was to explore the role of lutein, oxidized lutein (purified upon UV oxidation of lutein) and drug metformin, on mitochondrial biogenesis in HG-induced ARPE-19 cells and rat retina. Results showed higher uptake of lutein and oxidized lutein in ARPE-19 cells and rat retina of HG group than the control groups. Further, lutein and oxidized lutein augmented the AMPK phosphorylation and activation of mitochondrion signaling molecule TFAM (protein expression) and mRNA expression of PGC-1α, TFAM, and nuclear respiratory factor 1 (responsible for mitochondria biogenesis) along with lowered reactive oxygen species in HG compared with control and metformin groups. Higher mRNA expression of nicotinamide adenine dinucleotide dehydrogenase subunits mt-ND1, mt-ND4, mt-ND6, and cytochrome C that aid maintenance of mtDNA integrity was also evidenced. To conclude, lutein and oxidized lutein found to upsurge mitochondrial biogenesis in ARPE-19 cells and rat retina under HG, which may be due to upregulation of AMPK phosphorylation. Finally, lutein and oxidized lutein may provide a therapeutic basis to ameliorate HG-induced DR.

中文翻译：

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叶黄素通过AMPK激活上调PGC-1α，NRF1和TFAM表达，并下调ROS，以维持高血糖ARPE-19细胞和大鼠视网膜中的mtDNA完整性和线粒体生物发生。

高血糖（HG）影响视网膜中的细胞器，包括线粒体，通过下调核转录因子过氧化物酶体增殖物激活受体-γcoactivator-1（PGC-1α）和线粒体转录因子A（TFAM）来减少线粒体的生物发生。线粒体功能障碍与糖尿病性视网膜病（DR）有关。据报道，类胡萝卜素可调节HG中的线粒体生物发生。该研究的目的是探讨叶黄素，氧化的叶黄素（经叶黄素的紫外线氧化纯化）和药物二甲双胍对HG诱导的ARPE-19细胞和大鼠视网膜线粒体生物发生的作用。结果显示，HG组的ARPE-19细胞和大鼠视网膜中的叶黄素和氧化叶黄素的摄取高于对照组。进一步，叶黄素和氧化的叶黄素增强了AMPK的磷酸化和线粒体信号分子TFAM（蛋白质表达）的激活以及PGC-1α，TFAM和核呼吸因子1（负责线粒体生物发生）的mRNA表达，并降低了HG中的活性氧对照和二甲双胍组。还证实了烟酰胺腺嘌呤二核苷酸脱氢酶亚基mt-ND1，mt-ND4，mt-ND6和细胞色素C的较高的mRNA表达，这有助于维持mtDNA的完整性。总而言之，发现叶黄素和氧化叶黄素在HG下可促进ARPE-19细胞和大鼠视网膜中线粒体的生物发生，这可能是由于AMPK磷酸化的上调所致。最后，叶黄素和氧化的叶黄素可以为改善HG诱导的DR提供治疗基础。