Abstract Age-related macular degeneration (AMD) is a complex neurodegenerative disease, a main cause of vision loss in elderly people. The pathogenesis of dry AMD, the most common form of AMD (~ 80% cases), involves degenerative changes in the retinal pigment epithelium (RPE), which are closely associated with the age-associated impairments in autophagy. Reversion of these degenerative changes is considered as a promising approach for the treatment of this incurable disease. The purpose of our study was to assess the relationship between previously identified retinoprotective effects of the mitochondrial antioxidant plastoquinonyl-decyl-triphenylphosphonium (SkQ1) and its influence on the autophagy process in senescence-accelerated OXYS rats characterized by the development of AMD-like retinopathy (Wistar rats were used as a control). The treatment with SkQ1 (250 nmol/kg body weight) during the period of active disease progression (from 12 to 18 months of age) completely prevented progression of clinical manifestations of retinopathy in the OXYS rats, suppressed atrophic changes in the RPE cells and activated autophagy in the retina, which was evidenced by a significant decrease in the content of the multifunctional adapter protein p62/Sqstm1 and increase in the level of the Beclin1 gene mRNA. In general, the results obtained earlier and in the present study have shown that SkQ1 is a promising agent for prevention and suppression of AMD.

中文翻译：

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自噬作为线粒体靶向抗氧化剂 SkQ1 的视网膜保护作用的靶点

摘要 年龄相关性黄斑变性 (AMD) 是一种复杂的神经退行性疾病，是老年人视力丧失的主要原因。干性 AMD 是最常见的 AMD 形式（约 80% 的病例），其发病机制涉及视网膜色素上皮 (RPE) 的退行性变化，这与年龄相关的自噬损伤密切相关。逆转这些退行性变化被认为是治疗这种不治之症的有前途的方法。我们研究的目的是评估先前确定的线粒体抗氧化剂质体醌-癸基-三苯基鏻（SkQ1）的视网膜保护作用与其对以发生 AMD 样视网膜病变为特征的衰老加速 OXYS 大鼠自噬过程的影响之间的关系。 Wistar 大鼠用作对照）。在疾病活动期（12 至 18 个月大）期间用 SkQ1（250 nmol/kg 体重）治疗完全阻止了 OXYS 大鼠视网膜病变临床表现的进展，抑制了 RPE 细胞的萎缩变化并激活视网膜中的自噬，这可以通过多功能衔接蛋白 p62/Sqstm1 的含量显着减少和 Beclin1 基因 mRNA 水平的增加来证明。总的来说，早期和本研究中获得的结果表明，SkQ1 是一种有前途的预防和抑制 AMD 的药物。抑制 RPE 细胞的萎缩变化并激活视网膜中的自噬，这可以通过多功能衔接蛋白 p62/Sqstm1 的含量显着降低和 Beclin1 基因 mRNA 水平的增加来证明。总的来说，早期和本研究中获得的结果表明，SkQ1 是一种有前途的预防和抑制 AMD 的药物。抑制 RPE 细胞的萎缩变化并激活视网膜中的自噬，这可以通过多功能衔接蛋白 p62/Sqstm1 的含量显着降低和 Beclin1 基因 mRNA 水平的增加来证明。总的来说，早期和本研究中获得的结果表明，SkQ1 是一种有前途的预防和抑制 AMD 的药物。