Targeting tRNA‐Derived Non‐Coding RNA Alleviates Diabetes‐Induced Visual Impairment through Protecting Retinal Neurovascular Unit
Abstract Diabetes is a major risk factor for compromised visual health, leading to retinal vasculopathy and neuropathy, both of which are hallmarks of neurovascular unit dysfunction. Despite the critical impact of diabetic retinopathy, the precise mechanism underlying neurovascular coupling and effe...
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202411042 |
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| author | Jin Yao Wen Yao Jun‐Ya Zhu Yan Liu Jin‐Hong Liu Yu‐Ke Ji Xi‐Shen Ni Wan Mu Biao Yan |
| author_facet | Jin Yao Wen Yao Jun‐Ya Zhu Yan Liu Jin‐Hong Liu Yu‐Ke Ji Xi‐Shen Ni Wan Mu Biao Yan |
| author_sort | Jin Yao |
| collection | DOAJ |
| description | Abstract Diabetes is a major risk factor for compromised visual health, leading to retinal vasculopathy and neuropathy, both of which are hallmarks of neurovascular unit dysfunction. Despite the critical impact of diabetic retinopathy, the precise mechanism underlying neurovascular coupling and effective strategies to suppress neurovascular dysfunction remain unclear. In this study, the up‐regulation of a tRNA‐derived stress‐induced RNA, 5′tiRNA‐His‐GTG, in response to diabetic stress is revealed. 5′tiRNA‐His‐GTG directly regulates Müller glia action and indirectly alters endothelial angiogenic effects and retinal ganglion cell (RGC) survival in vitro. Downregulation of 5′tiRNA‐His‐GTG alleviates diabetes‐induced retinal neurovascular dysfunction, characterized by reduced retinal vascular dysfunction, decreased retinal neurodegeneration, and improved visually‐guided behaviors in vivo. Mechanistically, 5′tiRNA‐His‐GTG acts as a key regulator of retinal neurovascular dysfunction, primarily by modulating arachidonic acid (AA) metabolism via the CYPs pathway. The 5′tiRNA‐His‐GTG‐CYP2E1‐19(S)‐HETE signaling axis is identified as a key driver of retinal neurovascular dysfunction. Thus, targeting 5′tiRNA‐His‐GTG presents a promising therapeutic strategy for treating vasculopathy and neuropathy associated with diabetes mellitus. Modulating this novel signaling pathway can open up new avenues for intervention in diabetic retinopathy and its related complications. |
| format | Article |
| id | doaj-art-fb21f9654681415981e16485413a2d63 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-fb21f9654681415981e16485413a2d632025-01-09T11:44:46ZengWileyAdvanced Science2198-38442025-01-01121n/an/a10.1002/advs.202411042Targeting tRNA‐Derived Non‐Coding RNA Alleviates Diabetes‐Induced Visual Impairment through Protecting Retinal Neurovascular UnitJin Yao0Wen Yao1Jun‐Ya Zhu2Yan Liu3Jin‐Hong Liu4Yu‐Ke Ji5Xi‐Shen Ni6Wan Mu7Biao Yan8The Affiliated Eye Hospital Nanjing Medical University Nanjing 210000 ChinaThe Affiliated Eye Hospital Nanjing Medical University Nanjing 210000 ChinaThe Affiliated Eye Hospital Nanjing Medical University Nanjing 210000 ChinaThe Affiliated Eye Hospital Nanjing Medical University Nanjing 210000 ChinaThe Affiliated Eye Hospital Nanjing Medical University Nanjing 210000 ChinaThe Affiliated Eye Hospital Nanjing Medical University Nanjing 210000 ChinaThe Affiliated Eye Hospital Nanjing Medical University Nanjing 210000 ChinaDepartment of Ophthalmology Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200080 ChinaDepartment of Ophthalmology Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200080 ChinaAbstract Diabetes is a major risk factor for compromised visual health, leading to retinal vasculopathy and neuropathy, both of which are hallmarks of neurovascular unit dysfunction. Despite the critical impact of diabetic retinopathy, the precise mechanism underlying neurovascular coupling and effective strategies to suppress neurovascular dysfunction remain unclear. In this study, the up‐regulation of a tRNA‐derived stress‐induced RNA, 5′tiRNA‐His‐GTG, in response to diabetic stress is revealed. 5′tiRNA‐His‐GTG directly regulates Müller glia action and indirectly alters endothelial angiogenic effects and retinal ganglion cell (RGC) survival in vitro. Downregulation of 5′tiRNA‐His‐GTG alleviates diabetes‐induced retinal neurovascular dysfunction, characterized by reduced retinal vascular dysfunction, decreased retinal neurodegeneration, and improved visually‐guided behaviors in vivo. Mechanistically, 5′tiRNA‐His‐GTG acts as a key regulator of retinal neurovascular dysfunction, primarily by modulating arachidonic acid (AA) metabolism via the CYPs pathway. The 5′tiRNA‐His‐GTG‐CYP2E1‐19(S)‐HETE signaling axis is identified as a key driver of retinal neurovascular dysfunction. Thus, targeting 5′tiRNA‐His‐GTG presents a promising therapeutic strategy for treating vasculopathy and neuropathy associated with diabetes mellitus. Modulating this novel signaling pathway can open up new avenues for intervention in diabetic retinopathy and its related complications.https://doi.org/10.1002/advs.202411042diabetic retinopathyneuropathyneurovascular dysfunctiontRNA‐derived stress‐induced RNAsvasculopathy |
| spellingShingle | Jin Yao Wen Yao Jun‐Ya Zhu Yan Liu Jin‐Hong Liu Yu‐Ke Ji Xi‐Shen Ni Wan Mu Biao Yan Targeting tRNA‐Derived Non‐Coding RNA Alleviates Diabetes‐Induced Visual Impairment through Protecting Retinal Neurovascular Unit Advanced Science diabetic retinopathy neuropathy neurovascular dysfunction tRNA‐derived stress‐induced RNAs vasculopathy |
| title | Targeting tRNA‐Derived Non‐Coding RNA Alleviates Diabetes‐Induced Visual Impairment through Protecting Retinal Neurovascular Unit |
| title_full | Targeting tRNA‐Derived Non‐Coding RNA Alleviates Diabetes‐Induced Visual Impairment through Protecting Retinal Neurovascular Unit |
| title_fullStr | Targeting tRNA‐Derived Non‐Coding RNA Alleviates Diabetes‐Induced Visual Impairment through Protecting Retinal Neurovascular Unit |
| title_full_unstemmed | Targeting tRNA‐Derived Non‐Coding RNA Alleviates Diabetes‐Induced Visual Impairment through Protecting Retinal Neurovascular Unit |
| title_short | Targeting tRNA‐Derived Non‐Coding RNA Alleviates Diabetes‐Induced Visual Impairment through Protecting Retinal Neurovascular Unit |
| title_sort | targeting trna derived non coding rna alleviates diabetes induced visual impairment through protecting retinal neurovascular unit |
| topic | diabetic retinopathy neuropathy neurovascular dysfunction tRNA‐derived stress‐induced RNAs vasculopathy |
| url | https://doi.org/10.1002/advs.202411042 |
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