Abstract：
Minocycline, a broad-spectrum tetracycline antibiotic, has been shown to possess anti-inflammatory and antioxidative effects in various neurodegenerative diseases. However, its specific effects on retinitis pigmentosa (RP) have not been thoroughly investigated. Therefore, the objective of this study was to explore the potential role of minocycline in treating RP. In this investigation, we used rd1 to explore the antioxidant effect of minocycline in RP. Minocycline therapy effectively restored retinal function and structure in rd1 mice at 14 days postnatal. Additionally, minocycline inhibited the activation of microglia. Moreover, RNA sequencing analysis revealed a significant downregulation in the expression of mitochondrial genes within the retina of rd1 mice. Further KEGG and GO pathway analysis indicated impaired oxidative phosphorylation and electron transport chain processes. TEM confirmed the presence of damaged mitochondria in photoreceptors, while JC-1 staining demonstrated a decrease in mitochondrial membrane potential, accompanied by an increase in mitochondrial reactive oxygen species (ROS) levels. However, treatment with minocycline successfully reversed the abnormal expression of mitochondrial genes and reduced the levels of mitochondrial ROS, thereby providing protection against photoreceptor degeneration. Collectively, minocycline demonstrated the ability to rescue photoreceptor cells in RP by effectively modulating mitochondrial homeostasis and subsequently inflammation. These findings hold significant implications for the development of potential therapeutic strategies for RP.
摘要：
米诺环素,广谱四环素类抗生素,已被证明在各种神经退行性疾病中具有抗炎和抗氧化作用。然而,其对色素性视网膜炎（RP）的具体影响尚未得到彻底研究。因此,本研究的目的是探讨米诺环素在治疗RP中的潜在作用。在这次调查中,我们使用rd1来探讨米诺环素在RP中的抗氧化作用。米诺环素治疗在出生后14天有效地恢复rd1小鼠的视网膜功能和结构。此外,米诺环素抑制小胶质细胞的活化。此外，RNA测序分析揭示了rd1小鼠视网膜内线粒体基因表达的显著下调。进一步的KEGG和GO途径分析表明氧化磷酸化和电子传递链过程受损。TEM证实光感受器中存在受损的线粒体，而JC-1染色显示线粒体膜电位下降，伴随着线粒体活性氧（ROS）水平的增加。然而,米诺环素治疗成功逆转了线粒体基因的异常表达，降低了线粒体ROS的水平，从而提供针对感光体退化的保护。总的来说，米诺环素证明了通过有效调节线粒体稳态和随后的炎症来挽救RP中的感光细胞的能力。这些发现对RP潜在治疗策略的发展具有重要意义。
