1. Minocycline prevents photoreceptor degeneration in Retinitis pigmentosa through modulating mitochondrial homeostasis.
- Author
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Shi Y, Chen Y, Pan Y, Chen G, Xiao Z, Chen X, Wang M, and Liang D
- Subjects
- Animals, Mice, Retinal Degeneration drug therapy, Retinal Degeneration pathology, Retinal Degeneration metabolism, Disease Models, Animal, Mice, Inbred C57BL, Photoreceptor Cells, Vertebrate drug effects, Photoreceptor Cells, Vertebrate pathology, Photoreceptor Cells, Vertebrate metabolism, Membrane Potential, Mitochondrial drug effects, Microglia drug effects, Microglia metabolism, Retina drug effects, Retina pathology, Retina metabolism, Humans, Antioxidants pharmacology, Antioxidants therapeutic use, Minocycline pharmacology, Minocycline therapeutic use, Retinitis Pigmentosa drug therapy, Retinitis Pigmentosa metabolism, Mitochondria drug effects, Mitochondria metabolism, Homeostasis drug effects, Reactive Oxygen Species metabolism
- 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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