| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Costa, Bruna Lopes da Quinn, Peter M. J. Wu, Wen-Hsuan Liu, Siyuan Nolan, Nicholas D. Demirkol, Aykut Tsai, Yi-Ting Caruso, Salvatore Marco Cabral, Thiago Wang, Nan-Kai Tsang, Stephen H. |
| Abstract | Background Retinitis pigmentosa (RP) is a genetically heterogeneous group of degenerative disorders causing progressive vision loss due to photoreceptor death. RP affects other retinal cells, including the retinal pigment epithelium (RPE). MicroRNAs (miRs) are implicated in RP pathogenesis, and downregulating miR-181a/b has shown therapeutic benefit in RP mouse models by improving mitochondrial function. This study investigates the expression profile of miR-181a/b in RPE cells and the neural retina during RP disease progression. We also evaluate how miR-181a/b downregulation, by knocking out miR-181a/b-1 cluster in RPE cells, confers therapeutic efficacy in an RP mouse model and explore the mechanisms underlying this process. Results Our findings reveal distinct expression profiles, with downregulated miR-181a/b in RPE cells suggesting a protective response and upregulated miR-181a/b in the neural retina indicating a role in disease progression. We found that miR-181a/b-2, encoded in a separate genomic cluster, compensates for miR-181a/b-1 ablation in RPE cells at late time points. The transient downregulation of miR-181a/b in RPE cells at post-natal week 6 (PW6) led to improved RPE morphology, retarded photoreceptor degeneration and decreased RPE aerobic glycolysis. Conclusions Our study elucidates the underlying mechanisms associated with the therapeutic modulation of miR-181a/b, providing insights into the metabolic processes linked to its RPE-specific downregulation. Our data further highlights the impact of compensatory regulation between miR clusters with implications for the development of miR-based therapeutics. Graphical Abstract |
| Related Links | https://cellandbioscience.biomedcentral.com/counter/pdf/10.1186/s13578-024-01243-3.pdf |
| Ending Page | 20 |
| Page Count | 20 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 20453701 |
| DOI | 10.1186/s13578-024-01243-3 |
| Journal | Cell & Bioscience |
| Issue Number | 1 |
| Volume Number | 14 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-05-21 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Microbiology Stem Cells Neurobiology Proteomics MicroRNAs Metabolic reprogramming Retinal pigment epithelium Retinitis pigmentosa Aerobic glycolysis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry, Genetics and Molecular Biology |
| Journal Impact Factor | 6.1/2023 |
| 5-Year Journal Impact Factor | 7/2023 |
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