Flavonoids protect retinal ganglion cells from oxidative stress-induced death
Flavonoids protect retinal ganglion cells from oxidative stress-induced death
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DOI：
10.1167/iovs.05-0397
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发表时间：
2005-12-01
影响因子：
4.4
通讯作者：
Hanneken, A
中科院分区：
文献类型：
--
作者：
Maher, P;Hanneken, A
目的.越来越多的证据表明，氧化应激有助于许多眼部疾病的发病机制，包括青光眼和糖尿病视网膜病变。没有治疗方法可用于预防这些疾病中发生的神经元变性。本研究的目的是确定黄酮类化合物，水果和蔬菜中丰富的天然产物，是否可以保护视网膜神经节细胞免受氧化应激诱导的死亡。类黄酮保护永生化视网膜神经节细胞系RGC-5细胞的能力使用氧化应激诱导的细胞死亡的三种模型系统进行测试：谷胱甘肽（GSH）耗竭、叔丁基过氧化物（t-BOOH）处理和过氧化氢（H2 O2）处理。GSH耗竭通过涉及产生内源性活性氧（ROS）的途径引起视网膜神经节细胞死亡，而其他两种治疗使用外源性ROS来源。研究发现，特定的黄酮类化合物可以保护视网膜神经节细胞免受氧化应激诱导剂引起的细胞死亡，具有高水平的效力和低毒性。在GSH耗尽的情况下，不同的类黄酮可以在细胞死亡途径的不同步骤中发挥作用。几种保护性黄酮类化合物还诱导转录因子NF-E2相关因子2和2相抗氧化酶（例如血红素加氧酶1，抗氧化反应元件激活的标记物）的合成。结论。这些结果表明，某些黄酮类化合物可以作为视网膜神经节细胞的强效和有效的神经保护剂。
PURPOSE. Mounting evidence suggests that oxidative stress contributes to the pathogenesis of many ocular diseases, including glaucoma and diabetic retinopathy. No treatments are available to prevent the neuronal degeneration that occurs in these disorders. The purpose of this study was to determine whether flavonoids, natural products that are abundant in fruits and vegetables, can protect retinal ganglion cells from oxidative stress - induced death.METHODS. The ability of flavonoids to protect an immortalized retinal ganglion cell line, RGC-5 cells, was tested using three model systems of oxidative stress - induced cell death: glutathione (GSH) depletion, t-butyl peroxide (t-BOOH) treatment, and hydrogen peroxide (H2O2) treatment.RESULTS. GSH depletion causes retinal ganglion cell death by a pathway involving the production of endogenous reactive oxygen species (ROS), whereas the other two treatments use exogenous sources of ROS. It was found that specific flavonoids could protect retinal ganglion cells from cell death initiated by all three of the inducers of oxidative stress with high levels of potency and low toxicity. In the case of GSH depletion, different flavonoids could be shown to act at distinct steps in the cell death pathway. Several of the protective flavonoids also induced the synthesis of the transcription factor NF-E2-related factor 2 and phase 2 antioxidant enzymes such as heme oxygenase 1, markers for the activation of the antioxidant response element.CONCLUSIONS. These results suggest that certain flavonoids can function as potent and effective neuroprotective agents for retinal ganglion cells.