Data_Sheet_3_(–)-Epicatechin Provides Neuroprotection in Sodium Iodate-Induced Retinal Degeneration.DOCX

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.

氧化应激（oxidative stress）、线粒体功能损伤以及病理性淀粉样蛋白β(Aβ)沉积参与干性年龄相关性黄斑变性（age-related macular degeneration, AMD）的发病机制。天然黄酮类化合物(–)-表儿茶素（EC）是已知的抗氧化与神经保护活性物质，其在AMD中是否发挥治疗作用尚属未知。本研究旨在通过生物信息学、形态学与功能学方法，评估EC对碘酸钠(NaIO3)诱导的C57BL/6小鼠视网膜变性的干预效果及其分子机制。本研究证实，EC对视网膜无毒性作用，可改善视网膜变形与变薄。EC干预可阻断视网膜外层变性、减少玻璃膜疣样沉积物沉积，提升视网膜电图的b波振幅，抑制视网膜胶质增生，并改善线粒体的数量与质量。重要的是，EC可上调视神经萎缩蛋白1（OPA1）的蛋白表达水平，下调PTEN诱导激酶1（PINK1）的表达，表明EC可修复NaIO3诱导受损的线粒体融合过程。此外，EC可下调淀粉样前体蛋白（APP）与跨膜蛋白97（TMEM97）的表达水平，上调孕酮膜受体组件1（PGRMC1）的表达，并减少视网膜下Aβ沉积。本研究表明，EC可预防NaIO3诱导的视网膜变性，有望成为AMD极具潜力的治疗策略，其对病变的改善作用或与线粒体质量控制（mitochondrial quality control）及TMEM97/PGRMC1/Aβ信号通路密切相关。