源自脂肪间充质干细胞的细胞外囊泡通过激活 Nrf2 信号通路缓解视网膜色素上皮细胞的凋亡和氧化应激

IF 1.9 4区 医学 Q2 OPHTHALMOLOGY
Jin Sun Hwang, Hyun Beom Song, Geonhui Lee, Sangmoo Jeong, Dae Joong Ma
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引用次数: 0

摘要

目的:研究脂肪间充质干细胞衍生的细胞外囊泡(ASC-EVs)对暴露于过氧化氢(H2O2)应激的ARPE-19细胞的潜在保护作用,并评估其延缓皇家外科学院(RCS)大鼠视网膜变性的能力。方法:预处理 ARPE-19 细胞:一只眼睛接受磷酸盐缓冲盐水静脉注射,另一只眼睛接受ASC-EVs静脉注射。结果在细胞计数试剂盒-8测定中,ASC-EV预处理能明显抑制H2O2,在乳酸脱氢酶释放测定中也有效。它明显减少了早期细胞凋亡(Annexin V-荧光素异硫氰酸酯/碘化丙啶检测)和晚期细胞凋亡(末端脱氧核苷酸转移酶 dUTP Nick End Labeling 检测),同时显著降低了细胞内活性氧、谷胱甘肽水平和超氧化物歧化酶活性。经 ASC-EV 预处理后,NFE2L2、HMOX1 和 NQO1 mRNA 水平以及 Nrf2、HO-1 和 NQO1 蛋白水平均明显升高。与 ARPE-19 衍生的 EV 相比,ASC-EV 中有 11 个 miRNA 上调,34 个下调。在RCS大鼠中,玻璃体内注射ASC-EVs可显著保留核外层和感光节段,同时增加核Nrf2的表达,提高视网膜内层的HO-1和NQO1水平。注射ASC-EVs后1周,视网膜电图a波和b波振幅得到明显保护,但这种效果在2周后逐渐消失。结论ASC-EVs能减轻暴露于H2O2的ARPE-19细胞的凋亡和氧化应激,并通过miRNAs激活Nrf2通路暂时减缓RCS大鼠的视网膜退化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Extracellular Vesicles Derived from Adipose-Derived Mesenchymal Stem Cells Alleviate Apoptosis and Oxidative Stress of Retinal Pigment Epithelial Cells Through Activation of Nrf2 Signaling Pathway.

Purpose: To examine the potential protective effects of adipose-derived mesenchymal stem cell-derived extracellular vesicles (ASC-EVs) on ARPE-19 cells exposed to hydrogen peroxide (H2O2) stress and to evaluate their ability to delay retinal degeneration in Royal College of Surgeons (RCS) rats. Methods: ARPE-19 cells were pre-treated with ASC-EVs for 24 h, followed by exposure to 200 μM H2O2 for an additional 24 h. RCS rats received an intravitreal injection of phosphate-buffered saline in one eye and ASC-EVs in the other eye. Results: ASC-EV pretreatment significantly protected against H2O2 in the Cell Counting Kit-8 assay and was also effective in the lactate dehydrogenase-release assay. It notably reduced early apoptosis (Annexin V-fluorescein isothiocyanate/propidium iodide assay) and late apoptosis (Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling assay), while significantly decreasing intracellular reactive oxygen species, glutathione levels, and superoxide dismutase activity. NFE2L2, HMOX1, and NQO1 mRNA levels, along with Nrf2, HO-1, and NQO1 protein levels, were significantly elevated with ASC-EV pretreatment. Compared with ARPE-19-derived EVs, 11 miRNAs were upregulated and 34 were downregulated in ASC-EVs. In RCS rats, intravitreal injections of ASC-EVs led to significant preservation of the outer nuclear layer and photoreceptor segments, along with increased nuclear Nrf2 expression and elevated HO-1 and NQO1 levels in the inner retina. Eyes that received intravitreal injections of ASC-EVs demonstrated significantly preserved electroretinography a- and b-wave amplitudes at 1 week post-injection, though this effect faded by 2 weeks. Conclusions: ASC-EVs mitigated apoptosis and oxidative stress in ARPE-19 cells subjected to H2O2 exposure and temporarily slowed retinal degeneration in RCS rats via Nrf2 pathway activation by miRNAs.

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来源期刊
CiteScore
4.60
自引率
4.30%
发文量
72
审稿时长
1 months
期刊介绍: Journal of Ocular Pharmacology and Therapeutics is the only peer-reviewed journal that combines the fields of ophthalmology and pharmacology to enable optimal treatment and prevention of ocular diseases and disorders. The Journal delivers the latest discoveries in the pharmacokinetics and pharmacodynamics of therapeutics for the treatment of ophthalmic disorders. Journal of Ocular Pharmacology and Therapeutics coverage includes: Glaucoma Cataracts Retinal degeneration Ocular infection, trauma, and toxicology Ocular drug delivery and biotransformation Ocular pharmacotherapy/clinical trials Ocular inflammatory and immune disorders Gene and cell-based therapies Ocular metabolic disorders Ocular ischemia and blood flow Proliferative disorders of the eye Eyes on Drug Discovery - written by Gary D. Novack, PhD, featuring the latest updates on drug and device pipeline developments as well as policy/regulatory changes by the FDA.
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