中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (3): 989-999.doi: 10.4103/NRR.NRR-D-24-00794

• 综述:视神经损伤修复保护与再生 • 上一篇    下一篇

视神经损伤后的分子机制:转录组学视角下的神经修复策略

  

  • 出版日期:2026-03-15 发布日期:2025-07-02
  • 基金资助:
    此研究得到国家自然科学基金(82471123、82171053)、吉林省医药卫生人才专项(2024WSXK-E01)和吉林省自然科学基金(YDZJ202501ZYTS318)的资助。

Molecular mechanisms after optic nerve injury: Neurorepair strategies from a transcriptomic perspective

Xiaxue Chen, Muyang Wei, Guangyu Li*   

  1. Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin Province, China
  • Online:2026-03-15 Published:2025-07-02
  • Contact: Guangyu Li, MD, PhD, liguangyu@aliyun.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 82471123, 82171053; the Jilin Province Special Project for Talent in Medical and Health Sciences, No. 2024WSXK-E01; and the Natural Science Foundation of Jilin Province, YDZJ202501ZYTS318 (all to GL).

摘要:

视网膜神经节细胞是中枢神经系统的重要组成部分,其损伤常由创伤、缺血、青光眼等引起,导致不可逆的视力损害。研究发现,视神经压迫模型和青光眼模型是研究视网膜神经节细胞损伤的常用动物模型,尽管两者存在差异,但都会导致视网膜神经节细胞损伤。随着高通量技术的发展,微阵列分析、RNA测序和单细胞RNA测序等技术被广泛应用于描述视网膜神经节细胞损伤的转录组图谱,揭示了损伤背后的分子机制。这篇综述的主要目的是重点关注视神经压迫和青光眼模型,通过单细胞转录组学、转录组分析和芯片分析,描述视神经损伤和青光眼诱导的神经元变性的机制。在视神经压迫模型研究中,不同视网膜神经节细胞亚型在损伤后表现出不同的生存和再生能力,通过单细胞RNA测序技术鉴定出多个与视网膜神经节细胞保护和再生相关的基因,如Gal、Ucn和Anxa2等。在青光眼模型研究中,通过高通量测序技术揭示了高眼压条件下视网膜神经节细胞的转录组变化。研究发现了一些与免疫反应、氧化应激和细胞凋亡相关的基因,这些基因在视神经损伤后早期表达显著上调,可能参与了视网膜神经节细胞的神经保护和轴突再生过程。此外,通过CRISPR-Cas9筛选和ATAC-seq分析,鉴定出多个调控视网膜神经节细胞存活和轴突再生的关键转录因子,这些发现为青光眼的神经修复策略提供了新的潜在靶点。总之,单细胞转录组学技术为理解视神经损伤后的分子机制提供了前所未有的细节,有助于识别新的治疗靶点。未来研究者们需要结合先进的单细胞测序技术和多组学方法,深入研究视网膜神经节细胞损伤和再生的细胞特异性反应;利用计算模型和系统生物学方法,预测分子通路间的相互作用,为视神经再生和修复的临床研究提供指导。

https://orcid.org/0000-0002-6338-2507 (Guangyu Li)

关键词: 基因网, 青光眼, 芯片, 神经退行性变, 视神经挤压, 视神经再生, 视网膜神经节细胞, RNA测序, 单细胞RNA测序, 转录组

Abstract: Retinal ganglion cells, a crucial component of the central nervous system, are often affected by irreversible visual impairment due to various conditions, including trauma, tumors, ischemia, and glaucoma. Studies have shown that the optic nerve crush model and glaucoma model are commonly used to study retinal ganglion cell injury. While these models differ in their mechanisms, both ultimately result in retinal ganglion cell injury. With advancements in high-throughput technologies, techniques such as microarray analysis, RNA sequencing, and single-cell RNA sequencing have been widely applied to characterize the transcriptomic profiles of retinal ganglion cell injury, revealing underlying molecular mechanisms. This review focuses on optic nerve crush and glaucoma models, elucidating the mechanisms of optic nerve injury and neuron degeneration induced by glaucoma through single-cell transcriptomics, transcriptome analysis, and chip analysis. Research using the optic nerve crush model has shown that different retinal ganglion cell subtypes exhibit varying survival and regenerative capacities following injury. Single-cell RNA sequencing has identified multiple genes associated with retinal ganglion cell protection and regeneration, such as Gal, Ucn, and Anxa2. In glaucoma models, high-throughput sequencing has revealed transcriptomic changes in retinal ganglion cells under elevated intraocular pressure, identifying genes related to immune response, oxidative stress, and apoptosis. These genes are significantly upregulated early after optic nerve injury and may play key roles in neuroprotection and axon regeneration. Additionally, CRISPR-Cas9 screening and ATAC-seq analysis have identified key transcription factors that regulate retinal ganglion cell survival and axon regeneration, offering new potential targets for neurorepair strategies in glaucoma. In summary, single-cell transcriptomic technologies provide unprecedented insights into the molecular mechanisms underlying optic nerve injury, aiding in the identification of novel therapeutic targets. Future researchers should integrate advanced single-cell sequencing with multi-omics approaches to investigate cell-specific responses in retinal ganglion cell injury and regeneration. Furthermore, computational models and systems biology methods could help predict molecular pathways interactions, providing valuable guidance for clinical research on optic nerve regeneration and repair.

Key words: glaucoma, microarray, neurodegeneration, optic nerve crush, optic nerve regeneration, retinal ganglion cell, RNA sequencing, single-cell RNA sequencing, transcriptome