Abstract

Context

Oxidative injury in a high-glucose (HG) environment may be a mechanism of diabetic retinopathy (DR) and edaravone can protect retinal ganglion cells by scavenging ROS.

Objective

To explore the effect of edaravone on HG-induced injury.

Materials and methods

First, Müller cells were cultured by different concentrations of glucose for different durations to obtain a suitable culture concentrations and duration. Müller cells were then divided into Control, HG + Vehicle, HG + Eda-5 μM, HG + Eda-10 μM, HG + Eda-20 μM, and HG + Eda-40 μM groups. Cells were cultured by 20 mM glucose and different concentrations of edaravone for 72 h.

Results

The IC₅₀ of glucose at 12–72 h is 489.3, 103.5, 27.92 and 20.71 mM, respectively. When Müller cells were cultured in 20 mM glucose for 72 h, the cell viability was 52.3%. Edaravone significantly increased cell viability compared to Vehicle (68.4% vs 53.3%; 78.6% vs 53.3%). The EC₅₀ of edaravone is 34.38 μM. HG induced high apoptosis rate (25.5%), while edaravone (20 and 40 μM) reduced it to 12.5% and 6.89%. HG increased the DCF fluorescence signal (189% of Control) and decreased the mitochondrial membrane potential by 57%. Edaravone significantly decreased the DCF fluorescence signal (144% and 132% of Control) and recovered the mitochondrial membrane potential to 68% and 89% of Control. Furthermore, HG decreased the expression of TRX1, PGC-1α, NRF1 and TFAM, which were restored by edaravone.

Discussion and conclusion

These findings provide a new potential approach for the treatment of DR and indicated new molecular targets in the prevention of DR.

中文翻译：

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依达拉奉通过硫氧还蛋白 1 和 PGC-1α/NRF1/TFAM 通路预防高糖诱导的视网膜 Müller 细胞损伤

摘要

语境

高糖 (HG) 环境中的氧化损伤可能是糖尿病视网膜病变 (DR) 的一种机制，而依达拉奉可以通过清除 ROS 来保护视网膜神经节细胞。

客观的

探讨依达拉奉对HG致损伤的影响。

材料和方法

首先，将Müller细胞用不同浓度的葡萄糖培养不同的时间，以获得合适的培养浓度和时间。然后将 Müller 细胞分为对照、HG + 载体、HG + Eda-5 μM、HG + Eda-10 μM、HG + Eda-20 μM 和 HG + Eda-40 μM 组。细胞用 20 mM 葡萄糖和不同浓度的依达拉奉培养 72 小时。

结果

葡萄糖在 12-72 小时的 IC ₅₀分别为 489.3、103.5、27.92 和 20.71 mM。当 Müller 细胞在 20 mM 葡萄糖中培养 72 h 时，细胞活力为 52.3%。与载体相比，依达拉奉显着提高了细胞活力（68.4% 对 53.3%；78.6% 对 53.3%）。欧共体₅₀依达拉奉的浓度为 34.38 μM。HG 诱导高细胞凋亡率 (25.5%)，而依达拉奉 (20 和 40 μM) 将其降低至 12.5% 和 6.89%。HG 增加了 DCF 荧光信号（对照的 189%）并将线粒体膜电位降低了 57%。依达拉奉显着降低 DCF 荧光信号（对照的 144% 和 132%），并将线粒体膜电位恢复到对照的 68% 和 89%。此外，HG降低了TRX1、PGC-1α、NRF1和TFAM的表达，这些被依达拉奉恢复。

讨论与结论

这些发现为治疗 DR 提供了一种新的潜在方法，并指出了预防 DR 的新分子靶点。