中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (10): 5052-5062.doi: 10.4103/NRR.NRR-D-25-00295

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

RNA m6A参与调控视网膜星形胶质细胞发育性死亡和维持视网膜血管完整性

  

  • 出版日期:2026-10-15 发布日期:2026-06-15

The m6A writer VIRMA regulates the developmental elimination of retinal astrocytes and retinal vascular integrity maintenance.

Cuiting Wu1, 2, 3, #, Xiaoli Wu1, 3, #, Min Wu1, 3, 4, #, Xidan Zhou1, 3, #, Jie Tu3, Bin Shen5, Tao Zhou1, 3, 4, *   

  1. 1Shenzhen Neher Neural Plasticity Laboratory, Shenzhen Key Laboratory of Drug Addiction, the Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong Province, China; 
    2University of Chinese Academy of Sciences, Beijing, China; 
    3Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, Guangdong Province, China; 
    4Faculty of Life and Health Sciences, Shenzhen University of Advanced Technology, Shenzhen, Guangdong Province, China; 
    5State Key Laboratory of Reproductive Medicine and Offspring Health, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Gusu School, Nanjing Medical University, Nanjing, Jiangsu Province, China
  • Online:2026-10-15 Published:2026-06-15
  • Contact: Tao Zhou, PhD, zhoutao@suat-sz.ac.cn.
  • Supported by:
    This study was supported by Key-Area Research and Development Program of Guangdong Province, No. 2023B0303040004 (to TZ); Shenzhen Natural Science Foundation in Basic Research Fund, No. JCYJ20250604182944059 (to XW); the National Key R&D Program of China, No. 2018YFA0801401 (to TZ); the National Natural Science Foundation of China, Nos. 31922026, U20A2016 (to TZ), 32000675 (to MW); Basic and Applied Basic Research Foundation of Guangdong Province, Nos. 2019B151502007 (to TZ), 2020A1515110993 (to XZ); and Shenzhen Science and Technology Innovation Program, Nos. KQTD20210811090117032, ZDSYS20190902093601675 (to TZ).

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摘要：

星形胶质细胞网络的正常迁移和形成对视网膜血管和视觉功能至关重要。然而，其潜在机制尚不完全清楚。实验鉴定出VIRMA——N6-甲基腺苷（m6A）甲基转移酶复合物的核心支架蛋白——作为视网膜星形胶质细胞和视觉功能的新型调节因子。实验发现，在视网膜星形胶质细胞中条件性敲除VIRMA会阻碍小胶质细胞介导的吞噬清除，导致出生后发育过程中星形胶质细胞异常积累。值得注意的是，这种细胞稳态的破坏先于后续的病理性血管重塑。尽管初始视网膜血管化看似正常，但VIRMA缺失小鼠会出现持续的血管网不稳定，最终导致血管退化和不可逆的视觉障碍。机制上，单核转录组分析显示，VIRMA的缺失扰乱了多个参与细胞外基质组织和血管生成的m6A修饰基因的表达。这些分子变化与星形胶质细胞与内皮细胞之间的沟通受损相关，并导致血管稳态的破坏。总体而言，实验识别出VIRMA/m6A是调控视网膜星形胶质细胞发育性消除及神经血管完整性维持的新型调节因子。这项研究为星形胶质细胞相关视网膜病变提供了新见解，并突出了与血管相关的视觉障碍的潜在治疗靶点。


https://orcid.org/0009-0003-2184-3023 (Tao Zhou)

关键词: m6A, VIRMA, 视网膜, 星形胶质细胞消除, 发育, 小胶质细胞吞噬, 血管退化, 视力障碍, 单核RNA测序, 神经再生

Abstract: Proper migration and formation of the astrocyte network are essential for retinal vasculature and visual function. However, the underlying mechanisms remain incompletely understood. In the present study, we identified protein virilizer homolog VIR-like m6A methyltransferase associated (VIRMA)—the core scaffolding protein of the N6-methyladenosine (m6A) methyltransferase complex—as a novel regulator of retinal astrocytes and visual function. We demonstrated that the conditional knockout of VIRMA in retinal astrocytes impaired microglia-mediated phagocytic clearance, leading to abnormal astrocyte accumulation during postnatal development. Notably, this disruption in cellular homeostasis preceded subsequent pathological vascular remodeling. Although initial retinal vascularization appeared normal in VIRMA-deficient mice, persistent vascular plexus instability developed, ultimately leading to vessel regression and irreversible visual impairment. Mechanistically, single-nucleus transcriptomic analysis revealed that the loss of VIRMA disrupted the expression of multiple m6A-modified genes that are involved in extracellular matrix organization and angiogenesis. These molecular changes were correlated with impaired astrocyte–endothelial cell communication and contributed to the breakdown of vascular homeostasis. Collectively, our study identifies VIRMA/m6A as a novel regulator of the developmental elimination of retinal astrocytes and the maintenance of neurovascular integrity. This research provides new insights into astrocyte-related retinopathies and highlights potential therapeutic targets for vascular-associated visual disorders.

Key words: astrocyte elimination, development, N6-methyladenosine (m6A), microglial phagocytosis, retina, single-nucleus RNA sequencing, vessel regression, VIR-like m6A methyltransferase associated (VIRMA), visual impairment