TAUROURSODEOXYCHOLIC ACID PROTECTS RETINAL NEURAL CELLS FROM CELL DEATH INDUCED BY PROLONGED EXPOSURE TO ELEVATED GLUCOSE
TAUROURSODEOXYCHOLIC ACID PROTECTS RETINAL NEURAL CELLS FROM CELL DEATH INDUCED BY PROLONGED EXPOSURE TO ELEVATED GLUCOSE
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DOI：
10.1016/j.neuroscience.2013.08.053
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发表时间：
2013-12-03
期刊：
影响因子：
3.3
通讯作者：
Santiago, A. R.
中科院分区：
文献类型：
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作者：
Gaspar, J. M.;Martins, A.;Santiago, A. R.
糖尿病视网膜病变是西方国家成人致盲最常见的原因之一。虽然糖尿病视网膜病变被认为是一种血管疾病，但一些报告表明，视网膜神经元也会受到影响，导致视力丧失。牛磺酸脱氧胆酸(TUDCA)是一种内源性胆汁酸，已被证明在几种神经退行性疾病模型中具有神经保护作用，包括视网膜退行性疾病模型。由于高血糖被认为在视网膜细胞功能障碍和变性中起核心作用，是糖尿病视网膜病变的基础，本研究的目的是观察TUDCA对高糖暴露的大鼠视网膜神经元的神经保护作用。我们发现，TUDCA显著减少了高糖诱导的培养视网膜神经细胞的死亡。此外，TUDCA还部分阻止了线粒体中的凋亡诱导因子(AIF)的释放，以及随后AIF在细胞核中的聚集。氧化应激的生物标志物，如蛋白质羰基和活性氧的产生，在TUDCA处理后，与单独暴露在高葡萄糖浓度下的细胞相比显著减少。总之，TUDCA可保护培养的视网膜神经细胞免受葡萄糖浓度升高所致的细胞死亡，减少AIF的有丝分裂核转位。TUDCA的抗氧化作用可能是其细胞保护作用的原因。这些发现可能对糖尿病视网膜病变患者的治疗有一定的指导意义。(C)2013年IBRO。爱思唯尔有限公司出版。保留所有权利。
Diabetic retinopathy is one of the most frequent causes of blindness in adults in the Western countries. Although diabetic retinopathy is considered a vascular disease, several reports demonstrate that retinal neurons are also affected, leading to vision loss. Tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, has proven to be neuroprotective in several models of neurodegenerative diseases, including models of retinal degeneration. Since hyperglycemia is considered to play a central role in retinal cell dysfunction and degeneration, underlying the progression of diabetic retinopathy, the purpose of this study was to investigate the neuroprotective effects of TUDCA in rat retinal neurons exposed to elevated glucose concentration. We found that TUDCA markedly decreased cell death in cultured retinal neural cells induced by exposure to elevated glucose concentration. In addition, TUDCA partially prevented the release of apoptosis-inducing factor (AIF) from the mitochondria, as well as the subsequent accumulation of AIF in the nucleus. Biomarkers of oxidative stress, such as protein carbonyl groups and reactive oxygen species production, were markedly decreased after TUDCA treatment as compared to cells exposed to elevated glucose concentration alone. In conclusion, TUDCA protected retinal neural cell cultures from cell death induced by elevated glucose concentration, decreasing mito-nuclear translocation of AIF. The antioxidant properties of TUDCA might explain its cytoprotection. These findings may have relevance in the treatment of diabetic retinopathy patients. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.