(-)-Epicatechin Provides Neuroprotection in Sodium Iodate-Induced Retinal Degeneration.
(-)-Epicatechin Provides Neuroprotection in Sodium Iodate-Induced Retinal Degeneration.
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DOI：
10.3389/fmed.2022.879901
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发表时间：
2022
影响因子：
3.9
通讯作者：
中科院分区：
文献类型：
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作者：
氧化应激、线粒体损伤和病理性β淀粉样蛋白（Aβ）沉积参与干性年龄相关性黄斑变性（AMD）的发病机制。天然类黄酮(-)-表儿茶素（EC）是一种已知的抗氧化和神经保护化合物。EC是否在AMD中起治疗作用尚不清楚。在这项工作中，我们旨在通过生物信息学、形态学和功能方法评估EC对碘酸钠（NaIO3）诱导的C57BL/6小鼠视网膜变性的疗效和分子机制。我们证明了EC对视网膜没有毒性作用，可以改善视网膜变形和变薄。EC治疗可防止视网膜外变性，减少毒品样沉积物，增加视网膜电图b波振幅，阻断视网膜胶质细胞，增加线粒体的数量和质量。重要的是，EC增加了OPA1的蛋白表达，降低了PINK1的表达，这表明EC在NaIO3损伤的线粒体融合中发挥了作用。此外，EC下调APP和TMEM97水平，上调PGRMC1水平，减少视网膜下Aβ积累。本研究表明，EC可能成为一种有前景的治疗AMD的策略，它可以预防naio3诱导的视网膜变性，这种改善可能与线粒体质量控制和TMEM97/PGRMC1/ a β信号通路有关。
Oxidative stress, mitochondrial impairment, and pathological amyloid beta (Aβ) deposition are involved in the pathogenesis of dry age-related macular degeneration (AMD). The natural flavonoid (–)-epicatechin (EC) is known to be an antioxidant and neuroprotective compound. Whether EC plays a therapeutic role in AMD is unknown. In this work, we aimed to assess the efficacy and molecular mechanisms of EC against sodium iodate (NaIO3)-induced retinal degeneration in C57BL/6 mice via bioinformatic, morphological, and functional methods. We demonstrated that EC had no toxic effects on the retina and could ameliorate retinal deformation and thinning. EC treatment prevented outer retinal degeneration, reduced drusen-like deposits, increased b-wave amplitude in electroretinography, blocked retinal gliosis, and increased the number and quality of mitochondria. Importantly, EC increased the protein expression of OPA1 and decreased the expression of PINK1, indicating the role of EC in mitochondrial fusion that impaired by NaIO3. Moreover, EC downregulated APP and TMEM97 levels, upregulated PGRMC1 levels, and reduced subretinal Aβ accumulation. This study illustrated that EC, which may become a promising therapeutic strategy for AMD, prevented NaIO3-induced retinal degeneration, and this improvement may be associated with the mitochondrial quality control and the TMEM97/PGRMC1/Aβ signaling pathway.
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影响因子：
4.2
作者：
Feher, Janos;Kovacs, Illes;Gabrieli, Corrado Balacco
通讯作者：
Gabrieli, Corrado Balacco
影响因子：
5
作者：
Bucolo, C;Marrazzo, A;Drago, F
通讯作者：
Drago, F
影响因子：
16.2
作者：
Kamenetz, F;Tomita, T;Malinow, R
通讯作者：
Malinow, R
影响因子：
8.2
作者：
Al-Gayyar, M. M. H.;Matragoon, S.;El-Remessy, A. B.
通讯作者：
El-Remessy, A. B.
DOI：
10.1016/j.trci.2018.11.001
发表时间：
2019-01-01
影响因子：
4.8
作者：
Grundman, Michael;Morgan, Roger;Catalano, Susan M.
通讯作者：
Catalano, Susan M.