Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes.
Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes.
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DOI：
10.1007/s00125-009-1655-6
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发表时间：
2010-05
期刊：
影响因子：
8.2
通讯作者：
Tsubota, K.
中科院分区：
文献类型：
--
作者：
Sasaki, M.;Ozawa, Y.;Kurihara, T.;Kubota, S.;Yuki, K.;Noda, K.;Kobayashi, S.;Ishida, S.;Tsubota, K.
糖尿病视网膜病变是一种进行性神经退行性疾病，但其发病机制尚不清楚。在这里，我们重点关注视网膜中的氧化应激，并使用抗氧化剂叶黄素分析其对视网膜神经退行性变的影响。链脲佐菌素诱导的糖尿病C57 BL/6小鼠从糖尿病发作开始持续喂食叶黄素补充饮食或对照饮食，并记录其代谢数据。在1个月的糖尿病小鼠中，使用二氢乙锭测量视网膜中的活性氧（ROS），并通过视网膜电图评估视功能。还通过免疫印迹法测定了1个月糖尿病小鼠视网膜中活化的细胞外信号调节激酶（ERK）、突触素和脑源性神经营养因子（BDNF）的水平。在4个月糖尿病小鼠的视网膜切片中，分析组织学变化、切割的caspase-3和TUNEL染色。叶黄素不影响糖尿病小鼠的代谢状态，但它可以防止视网膜中ROS的产生和糖尿病引起的视力损害。ERK激活，随后的突触素减少，和BDNF耗尽在糖尿病视网膜都阻止叶黄素。后来，在4个月的糖尿病小鼠，减少的厚度内丛状和核层，神经节细胞的数量，以及增加裂解的半胱天冬酶-3-和TUNEL阳性细胞，避免了在视网膜中的叶黄素喂养的小鼠。结果表明，在糖尿病视网膜中具有神经退行性影响的局部氧化应激可通过持续摄入叶黄素补充饮食来预防。抗氧化剂叶黄素可能是一种潜在的治疗方法，以保护糖尿病的视觉功能。
Diabetic retinopathy is a progressive neurodegenerative disease, but the underlying mechanism is still obscure. Here, we focused on oxidative stress in the retina, and analysed its influence on retinal neurodegeneration, using an antioxidant, lutein. C57BL/6 mice with streptozotocin-induced diabetes were constantly fed either a lutein-supplemented diet or a control diet from the onset of diabetes, and their metabolic data were recorded. In 1-month-diabetic mice, reactive oxygen species (ROS) in the retina were measured using dihydroethidium and visual function was evaluated by electroretinograms. Levels of activated extracellular signal-regulated kinase (ERK), synaptophysin and brain-derived neurotrophic factor (BDNF) were also measured by immunoblotting in the retina of 1-month-diabetic mice. In the retinal sections of 4-month-diabetic mice, histological changes, cleaved caspase-3 and TUNEL staining were analysed. Lutein did not affect the metabolic status of the diabetic mice, but it prevented ROS generation in the retina and the visual impairment induced by diabetes. ERK activation, the subsequent synaptophysin reduction, and the BDNF depletion in the diabetic retina were all prevented by lutein. Later, in 4-month-diabetic mice, a decrease in the thickness of the inner plexiform and nuclear layers, and ganglion cell number, together with increase in cleaved caspase-3- and TUNEL-positive cells, were avoided in the retina of lutein-fed mice. The results indicated that local oxidative stress that has a neurodegenerative influence in the diabetic retina is prevented by constant intake of a lutein-supplemented diet. The antioxidant, lutein may be a potential therapeutic approach to protect visual function in diabetes.
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影响因子：
2.9
作者：
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通讯作者：
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影响因子：
7.1
作者：
Broekmans, WMR;Berendschot, TTJM;van Poppel, G
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影响因子：
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作者：
Barber, AJ;Lieth, E;Gardner, TW
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DOI：
10.1161/atvbaha.107.151431
发表时间：
2007-12-01
影响因子：
8.7
作者：
Izumi-Nagai, Kanako;Nagai, Norihiro;Ishida, Susumu
通讯作者：
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