中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (11): 2522-2531.doi: 10.4103/1673-5374.389363

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

急性高眼压视网膜单细胞RNA测序：揭示高眼压诱导视网膜损伤的分子机制

  

  • 出版日期:2024-11-15 发布日期:2024-03-29
  • 基金资助:
    国家自然科学基金项目（82371051），北京市自然科学基金项目（7212092），首都健康改善与研究基金项目（2022-2-5041），首都医科大学附属北京康复医院科技发展基金项目(2021R-001)

Single-cell RNA sequencing analysis of the retina under acute high intraocular pressure

Shaojun Wang1, #, Siti Tong1, #, Xin Jin1, Na Li1, Pingxiu Dang1, Yang Sui1, Ying Liu2, *, Dajiang Wang1, *   

  1. 1Division of Ophthalmology, The Third Medical Center of PLA General Hospital, Beijing, China; 2Department of Ophthalmology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
  • Online:2024-11-15 Published:2024-03-29
  • Contact: Dajiang Wang, MD, glaucomawang@163.com; Ying Liu, MD, liuying5322@163.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 82371051 (to DW); the Natural Science Foundation of Beijing, No. 7212092 (to DW); the Capital’s Funds for Health Improvement and Research, No. 2022-2-5041 (to DW); and the Fund of Science and Technology Development of Beijing Rehabilitation Hospital, Capital Medical University, No. 2021R-001 (to YL).

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摘要：

在原发性和继发性青光眼疾病中，高眼压会导致视网膜神经节细胞损伤，而目前对于高眼压视网膜细胞的全景式分子特征尚不清楚。为此，实验通过注射交联透明质酸水凝胶（Healaflow®）建立了急性高血压大鼠模型，然后使用单细胞RNA测序来描述高眼压下视网膜的细胞组成和分子图谱。结果可见，共鉴定出12种细胞类型，包括视网膜色素上皮细胞、视杆细胞、双极细胞、Müller细胞、小胶质细胞、视锥细胞、视网膜节细胞、内皮细胞、视网膜祖细胞、少突胶质细胞、周细胞和成纤维细胞。细胞比例分析显示高眼压组中视网膜各细胞比例发生明显变化，其中节细胞减少了23%。苏木精-伊红染色和TUNEL染色结果也证实了高眼压下视网膜神经节细胞的损伤。提取视网膜神经节细胞数据，并对其差异基因明显的3号亚群进行分析，发现与神经元迁移和粘附相关基因B3gat2上调，而参与抑制炎症的基因Tsc22d下调。此次研究首次揭示了高眼压下视网膜的景观图，并揭示了细胞间的相互作用。这些数据有助于理解高眼压诱导视网膜损伤的分子机制以及开发新的高眼压损伤疾病治疗方法。

https://orcid.org/0000-0001-8521-8006 (Dajiang Wang); https://orcid.org/0000-0003-1470-2583 (Ying Liu)

关键词: 高眼压, 眼压, 青光眼, 小胶质细胞, 单细胞RNA测序, 视网膜, 神经节细胞, 视网膜变性, 轴突变性, 感光细胞, 细胞凋亡

Abstract: High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases, yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown. Rat models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel (Healaflow®). Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular pressure. Our results identified a total of 12 cell types, namely retinal pigment epithelial cells, rod-photoreceptor cells, bipolar cells, Müller cells, microglia, cone-photoreceptor cells, retinal ganglion cells, endothelial cells, retinal progenitor cells, oligodendrocytes, pericytes, and fibroblasts. The single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells, with ganglion cells decreased by 23%. Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular pressure. We extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct expression. We found upregulation of the B3gat2 gene, which is associated with neuronal migration and adhesion, and downregulation of the Tsc22d gene, which participates in inhibition of inflammation. This study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular pressure. These data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.

Key words: apoptosis, axon degeneration, high intraocular pressure, microglia, ocular hypertension, photoreceptor cells, retina, retinal degeneration, retinal ganglion cells, single-cell RNA sequencing