Co-targeting of glial activation and inflammation by tsRNA-Gln-i-0095 for treating retinal ischemic pathologies
Abstract Ischemic retinopathies are the major causes of blindness, yet effective early-stage treatments remain limited due to an incomplete understanding of the underlying molecular mechanisms. Significant changes in gene expression often precede structural and functional alterations. Transfer RNA (...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-024-02013-x |
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| author | Ying Zhang Yan Ma Yu-Ke Ji Yi-Fei Jiang Duo Li Wan Mu Mu-Di Yao Jin Yao Biao Yan |
| author_facet | Ying Zhang Yan Ma Yu-Ke Ji Yi-Fei Jiang Duo Li Wan Mu Mu-Di Yao Jin Yao Biao Yan |
| author_sort | Ying Zhang |
| collection | DOAJ |
| description | Abstract Ischemic retinopathies are the major causes of blindness, yet effective early-stage treatments remain limited due to an incomplete understanding of the underlying molecular mechanisms. Significant changes in gene expression often precede structural and functional alterations. Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are emerging as novel gene regulators, involved in various biological processes and human diseases. In this study, tsRNA-Gln-i-0095 was identified as a novel regulator, which was significantly upregulated in retinal ischemia/reperfusion (I/R) injury. Reducing the levels of tsRNA-Gln-i-0095 suppressed reactive gliosis, lowered inflammatory cytokine levels, and protected retinal ganglion cells from I/R injury. These effects led to reduced structural and functional damage, inhibited glial activation and inflammation, and enhanced neuronal function. Mechanistically, tsRNA-Gln-i-0095 downregulated the expression of NFIA and TGFBR2 through a miRNA-like mechanism. Collectively, this study highlights the potential of targeting tsRNA-Gln-i-0095 as a novel therapeutic approach to reduce retinal I/R injury and preserve visual function. Graphical abstract |
| format | Article |
| id | doaj-art-33db56d9f89b4d7fb2060afef724d68b |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-33db56d9f89b4d7fb2060afef724d68b2025-01-12T12:32:55ZengBMCCell Communication and Signaling1478-811X2025-01-0123111910.1186/s12964-024-02013-xCo-targeting of glial activation and inflammation by tsRNA-Gln-i-0095 for treating retinal ischemic pathologiesYing Zhang0Yan Ma1Yu-Ke Ji2Yi-Fei Jiang3Duo Li4Wan Mu5Mu-Di Yao6Jin Yao7Biao Yan8The Affiliated Eye Hospital, Nanjing Medical UniversityThe Affiliated Eye Hospital, Nanjing Medical UniversityThe Affiliated Eye Hospital, Nanjing Medical UniversityThe Affiliated Eye Hospital, Nanjing Medical UniversityThe Affiliated Eye Hospital, Nanjing Medical UniversityEye Institute, Department of Ophthalmology, Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan UniversityDepartment of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong UniversityThe Affiliated Eye Hospital, Nanjing Medical UniversityDepartment of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract Ischemic retinopathies are the major causes of blindness, yet effective early-stage treatments remain limited due to an incomplete understanding of the underlying molecular mechanisms. Significant changes in gene expression often precede structural and functional alterations. Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are emerging as novel gene regulators, involved in various biological processes and human diseases. In this study, tsRNA-Gln-i-0095 was identified as a novel regulator, which was significantly upregulated in retinal ischemia/reperfusion (I/R) injury. Reducing the levels of tsRNA-Gln-i-0095 suppressed reactive gliosis, lowered inflammatory cytokine levels, and protected retinal ganglion cells from I/R injury. These effects led to reduced structural and functional damage, inhibited glial activation and inflammation, and enhanced neuronal function. Mechanistically, tsRNA-Gln-i-0095 downregulated the expression of NFIA and TGFBR2 through a miRNA-like mechanism. Collectively, this study highlights the potential of targeting tsRNA-Gln-i-0095 as a novel therapeutic approach to reduce retinal I/R injury and preserve visual function. Graphical abstracthttps://doi.org/10.1186/s12964-024-02013-xIschemic/reperfusion injuryMüller cellsRetinal ganglion cellstsRNAReactive gliosis |
| spellingShingle | Ying Zhang Yan Ma Yu-Ke Ji Yi-Fei Jiang Duo Li Wan Mu Mu-Di Yao Jin Yao Biao Yan Co-targeting of glial activation and inflammation by tsRNA-Gln-i-0095 for treating retinal ischemic pathologies Cell Communication and Signaling Ischemic/reperfusion injury Müller cells Retinal ganglion cells tsRNA Reactive gliosis |
| title | Co-targeting of glial activation and inflammation by tsRNA-Gln-i-0095 for treating retinal ischemic pathologies |
| title_full | Co-targeting of glial activation and inflammation by tsRNA-Gln-i-0095 for treating retinal ischemic pathologies |
| title_fullStr | Co-targeting of glial activation and inflammation by tsRNA-Gln-i-0095 for treating retinal ischemic pathologies |
| title_full_unstemmed | Co-targeting of glial activation and inflammation by tsRNA-Gln-i-0095 for treating retinal ischemic pathologies |
| title_short | Co-targeting of glial activation and inflammation by tsRNA-Gln-i-0095 for treating retinal ischemic pathologies |
| title_sort | co targeting of glial activation and inflammation by tsrna gln i 0095 for treating retinal ischemic pathologies |
| topic | Ischemic/reperfusion injury Müller cells Retinal ganglion cells tsRNA Reactive gliosis |
| url | https://doi.org/10.1186/s12964-024-02013-x |
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