Single‐cell RNA sequencing of retina revealed novel transcriptional landscape in high myopia and underlying cell‐type‐specific mechanisms
Abstract High myopia is a leading cause of blindness worldwide with increasing prevalence. Retina percepts visual information and triggers myopia development, but the underlying etiology is not fully understood because of cellular heterogeneity. In this study, single‐cell RNA sequencing analysis was...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.372 |
| _version_ | 1797659206728286208 |
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| author | Yunqian Yao Zhenhua Chen Qingfeng Wu Yi Lu Xingtao Zhou Xiangjia Zhu |
| author_facet | Yunqian Yao Zhenhua Chen Qingfeng Wu Yi Lu Xingtao Zhou Xiangjia Zhu |
| author_sort | Yunqian Yao |
| collection | DOAJ |
| description | Abstract High myopia is a leading cause of blindness worldwide with increasing prevalence. Retina percepts visual information and triggers myopia development, but the underlying etiology is not fully understood because of cellular heterogeneity. In this study, single‐cell RNA sequencing analysis was performed on retinas of mouse highly myopic and control eyes to dissect the involvement of each cell type during high myopia progression. For highly myopic photoreceptors, Hk2 inhibition underlying metabolic remodeling from aerobic glycolysis toward oxidative phosphorylation and excessive oxidative stress was identified. Importantly, a novel Apoe+ rod subpopulation was specifically identified in highly myopic retina. In retinal neurons of highly myopic eyes, neurodegeneration was generally discovered, and the imbalanced ON/OFF signaling driven by cone‐bipolar cells and the downregulated dopamine receptors in amacrine cells were among the most predominant findings, indicating the aberrant light processing in highly myopic eyes. Besides, microglia exhibited elevated expression of cytokines and TGF‐β receptors, suggesting enhanced responses to inflammation and the growth‐promoting states involved in high myopia progression. Furthermore, cell–cell communication network revealed attenuated neuronal interactions and increased glial/vascular interactions in highly myopic retinas. In conclusion, this study outlines the transcriptional landscape of highly myopic retina, providing novel insights into high myopia development and prevention. |
| first_indexed | 2024-03-11T18:10:33Z |
| format | Article |
| id | doaj.art-c768474db3344e61896b60ce2eb594bf |
| institution | Directory Open Access Journal |
| issn | 2688-2663 |
| language | English |
| last_indexed | 2024-03-11T18:10:33Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj.art-c768474db3344e61896b60ce2eb594bf2023-10-16T15:20:40ZengWileyMedComm2688-26632023-10-0145n/an/a10.1002/mco2.372Single‐cell RNA sequencing of retina revealed novel transcriptional landscape in high myopia and underlying cell‐type‐specific mechanismsYunqian Yao0Zhenhua Chen1Qingfeng Wu2Yi Lu3Xingtao Zhou4Xiangjia Zhu5Eye Institute and Department of Ophthalmology Eye & ENT Hospital Fudan University Shanghai ChinaState Key Laboratory of Molecular Development Biology Chinese Academy of Sciences Institute of Genetics and Developmental Biology Beijing ChinaState Key Laboratory of Molecular Development Biology Chinese Academy of Sciences Institute of Genetics and Developmental Biology Beijing ChinaEye Institute and Department of Ophthalmology Eye & ENT Hospital Fudan University Shanghai ChinaEye Institute and Department of Ophthalmology Eye & ENT Hospital Fudan University Shanghai ChinaEye Institute and Department of Ophthalmology Eye & ENT Hospital Fudan University Shanghai ChinaAbstract High myopia is a leading cause of blindness worldwide with increasing prevalence. Retina percepts visual information and triggers myopia development, but the underlying etiology is not fully understood because of cellular heterogeneity. In this study, single‐cell RNA sequencing analysis was performed on retinas of mouse highly myopic and control eyes to dissect the involvement of each cell type during high myopia progression. For highly myopic photoreceptors, Hk2 inhibition underlying metabolic remodeling from aerobic glycolysis toward oxidative phosphorylation and excessive oxidative stress was identified. Importantly, a novel Apoe+ rod subpopulation was specifically identified in highly myopic retina. In retinal neurons of highly myopic eyes, neurodegeneration was generally discovered, and the imbalanced ON/OFF signaling driven by cone‐bipolar cells and the downregulated dopamine receptors in amacrine cells were among the most predominant findings, indicating the aberrant light processing in highly myopic eyes. Besides, microglia exhibited elevated expression of cytokines and TGF‐β receptors, suggesting enhanced responses to inflammation and the growth‐promoting states involved in high myopia progression. Furthermore, cell–cell communication network revealed attenuated neuronal interactions and increased glial/vascular interactions in highly myopic retinas. In conclusion, this study outlines the transcriptional landscape of highly myopic retina, providing novel insights into high myopia development and prevention.https://doi.org/10.1002/mco2.372glucose metabolismhigh myopiamicrogliaON/OFF pathwaysretinasingle‐cell RNA sequencing |
| spellingShingle | Yunqian Yao Zhenhua Chen Qingfeng Wu Yi Lu Xingtao Zhou Xiangjia Zhu Single‐cell RNA sequencing of retina revealed novel transcriptional landscape in high myopia and underlying cell‐type‐specific mechanisms MedComm glucose metabolism high myopia microglia ON/OFF pathways retina single‐cell RNA sequencing |
| title | Single‐cell RNA sequencing of retina revealed novel transcriptional landscape in high myopia and underlying cell‐type‐specific mechanisms |
| title_full | Single‐cell RNA sequencing of retina revealed novel transcriptional landscape in high myopia and underlying cell‐type‐specific mechanisms |
| title_fullStr | Single‐cell RNA sequencing of retina revealed novel transcriptional landscape in high myopia and underlying cell‐type‐specific mechanisms |
| title_full_unstemmed | Single‐cell RNA sequencing of retina revealed novel transcriptional landscape in high myopia and underlying cell‐type‐specific mechanisms |
| title_short | Single‐cell RNA sequencing of retina revealed novel transcriptional landscape in high myopia and underlying cell‐type‐specific mechanisms |
| title_sort | single cell rna sequencing of retina revealed novel transcriptional landscape in high myopia and underlying cell type specific mechanisms |
| topic | glucose metabolism high myopia microglia ON/OFF pathways retina single‐cell RNA sequencing |
| url | https://doi.org/10.1002/mco2.372 |
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