Resveratrol protects retinal ganglion cells against ischemia induced damage by increasing Opa1 expression.

Resveratrol protects retinal ganglion cells against ischemia induced damage by increasing Opa1 expression.
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白藜芦醇通过增加 Opa1 表达来保护视网膜神经节细胞免受缺血引起的损伤

DOI:
10.3892/ijmm.2020.4711
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发表时间:
2020-11
影响因子:
5.4
通讯作者:
Zhang X
Zhang X
中科院分区:
医学3区
文献类型:
--
作者:
Pang Y;Qin M;Hu P;Ji K;Xiao R;Sun N;Pan X;Zhang X

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特发性视网膜神经节细胞(RGCs)的丧失导致不可逆的视力缺陷,被认为是青光眼的主要特征。然而,在RGC神经保护方面,有效的治疗策略仍然难以捉摸。在本研究中,我们研究了白藜芦醇对RGC细胞凋亡的保护作用及其作用机制,并特别强调了视神经萎缩1 (Opa1)的功能。在缺血/再灌注(I/R)损伤模型中,观察到视网膜明显变薄,RGCs明显凋亡,Opa1表达降低,长Opa1亚型与短Opa1亚型比值(L-Opa1/S-Opa1比值)降低,白藜芦醇可逆转这些变化。血清剥夺导致R28细胞活力、超氧化物歧化酶(SOD)活性、Opa1表达和诱导凋亡降低,白藜芦醇处理也部分逆转了这一变化。综上所述,本研究结果表明,白藜芦醇治疗可显著降低I/R损伤和血清剥夺模型的视网膜损伤和RGC凋亡。此外,白藜芦醇逆转了下调的Opa1表达,降低了SOD活性。机制上,白藜芦醇通过调节L-Opa1/S-Opa1比值影响线粒体动力学。因此,这些观察结果表明,白藜芦醇可能在未来表现出作为RGC损伤治疗剂的潜力。
Loss of idiopathic retinal ganglion cells (RGCs) leads to irreversible vision defects and is considered the primary characteristic of glaucoma. However, effective treatment strategies in terms of RGC neuroprotection remain elusive. In the present study, the protective effects of resveratrol on RGC apoptosis, and the mechanisms underlying its effects were investigated, with a particular emphasis on the function of optic atrophy 1 (Opa1). In an ischemia/reperfusion (I/R) injury model, the notable thinning of the retina, significant apoptosis of RGCs, reduction in Opa1 expression and long Opa1 isoform to short Opa1 isoform ratios (L-Opa1/S-Opa1 ratio) were observed, all of which were reversed by resveratrol administration. Serum deprivation resulted in reductions in R28 cell viability, superoxide dismutase (SOD) activity, Opa1 expression and induced apoptosis, which were also partially reversed by resveratrol treatment. To conclude, results from the present study suggest that resveratrol treatment significantly reduced retinal damage and RGC apoptosis in I/R injury and serum deprivation models. In addition, resveratrol reversed the downregulated expression of Opa1 and reduced SOD activity. Mechanistically, resveratrol influenced mitochondrial dynamics by regulating the L-Opa1/S-Opa1 ratio. Therefore, these observations suggest that resveratrol may exhibit potential as a therapeutic agent for RGC damage in the future.
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