Effect of Ubiquinol on Glaucomatous Neurodegeneration and Oxidative Stress: Studies for Retinal Ganglion Cell Survival and/or Visual Function.
Effect of Ubiquinol on Glaucomatous Neurodegeneration and Oxidative Stress: Studies for Retinal Ganglion Cell Survival and/or Visual Function.
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DOI：
10.3390/antiox9100952
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发表时间：
2020-10-03
期刊：
影响因子：
--
通讯作者：
Ju WK
中科院分区：
文献类型：
--
作者：
Edwards G;Lee Y;Kim M;Bhanvadia S;Kim KY;Ju WK
氧化应激是脑水肿性神经退行性变的主要原因之一。泛醇促进视网膜神经节细胞（RGC）对脑水肿损伤如氧化应激的存活。在这里，我们研究了泛醇对青光眼和氧化应激小鼠模型中RGC存活和/或视觉功能的影响。DBA/2 J和年龄匹配的DBA/2 J-Gpnmb+（D2-Gpnmb+）（其不发展眼内压升高）或C57 BL/6 J小鼠每天用泛醇（1%）或对照饮食喂养5或2个月。我们通过Brn 3a免疫组化评估RGC存活率，并测量活性和总BAX、过氧化物酶体增殖物激活受体-γ共激活因子1α、转录因子A（TFAM）和氧化磷酸化（OXPHOS）复合物蛋白的表达水平。在百草枯注射诱导氧化应激后，我们还评估了视觉功能。在青光眼视网膜中，泛醇补充显著促进RGC存活，阻断BAX活化并增加TFAM和OXPHOS复合物II蛋白表达。此外，泛醇补充改善氧化应激诱导的视觉功能障碍。这些发现表明，泛醇通过增加TFAM表达和OXPHOS复合物II活性促进RGC存活，并且泛醇增强RGC存活并保护视觉功能对抗氧化应激。我们认为泛醇具有治疗氧化应激相关性神经退行性变的潜力。
Oxidative stress is one of major causal factors in glaucomatous neurodegeneration. Ubiquinol promotes retinal ganglion cell (RGC) survival against glaucomatous insults such as oxidative stress. Here we investigated the effect of ubiquinol on RGC survival and/or visual function in mouse models of glaucoma and oxidative stress. DBA/2J and age-matched DBA/2J-Gpnmb+ (D2-Gpnmb+), which do not develop intraocular pressure elevation, or C57BL/6J mice were fed with ubiquinol (1%) or control diet daily for 5 or 2 months. We assessed RGC survival by Brn3a immunohistochemistry and measured expression levels of active and total BAX, peroxisome proliferator-activated receptor-gamma coactivator 1α, transcription factor A (TFAM) and oxidative phosphorylation (OXPHOS) complex protein. Following induction of oxidative stress by paraquat injection, we also assessed visual function. In glaucomatous retina, ubiquinol supplementation significantly promoted RGC survival, blocked BAX activation and increased TFAM and OXPHOS complex II protein expression. Also, ubiquinol supplementation ameliorated oxidative stress-induced visual dysfunction. These findings indicate that ubiquinol promotes RGC survival by increasing TFAM expression and OXPHOS complex II activity in glaucomatous neurodegeneration, and that ubiquinol enhances RGC survival and preserves visual function against oxidative stress. We propose that ubiquinol has a therapeutic potential for treating oxidative stress-associated glaucomatous neurodegeneration.
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影响因子：
7.1
作者：
Fernandez-Marcos, Pablo J.;Auwerx, Johan
通讯作者：
Auwerx, Johan
DOI：
10.1073/pnas.87.12.4879
发表时间：
1990-06-01
影响因子：
11.1
作者：
FREI, B;KIM, MC;AMES, BN
通讯作者：
AMES, BN
影响因子：
3.5
作者：
Ekstrand, MI;Falkenberg, M;Larsson, NG
通讯作者：
Larsson, NG
DOI：
10.1016/j.bbrc.2018.08.016
发表时间：
2018-09-18
影响因子：
3.1
作者：
Ju WK;Shim MS;Kim KY;Bu JH;Park TL;Ahn S;Weinreb RN
通讯作者：
Weinreb RN
影响因子：
56.9
作者：
Antonsson, B;Conti, F;Martinou, JC
通讯作者：
Martinou, JC