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 (2): 811-820.doi: 10.4103/NRR.NRR-D-24-00621

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

斑马鱼视神经再生涉及驻留细胞和视网膜少突胶质细胞

  

  • 出版日期:2026-02-15 发布日期:2025-05-24

Zebrafish optic nerve regeneration involves resident and retinal oligodendrocytes

Cristina Pérez-Montes1, 2, 3, Rosalía Hernández-García1 , Jhoana Paola Jiménez-Cubides1 , Laura DeOliveira-Mello4 , Almudena Velasco1, 3, 5, Rosario Arévalo1, 3, 5, Marina García-Macia3, 6, 7, *, Adrián Santos-Ledo1, 2, 3, *   

  1. 1 Institute of Neuroscience of Castilla y León (INCyL), Salamanca, Spain;  2 Department of Human Anatomy and Histology, University of Salamanca, Salamanca, Spain;  3 Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain;  4 Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland;  5 Department of Cell Biology and Pathology, University of Salamanca, Salamanca, Spain;  6 Institute of Functional Biology and Genomics (IBFG), University of Salamanca/CSIC, Salamanca, Spain;  7 Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca, Spain
  • Online:2026-02-15 Published:2025-05-24
  • Contact: Adrián Santos-Ledo, PhD, santosledo@usal.es; Marina García-Macia, PhD, marinagarciamacia@usal.es.
  • Supported by:
    This study was supported by the Lanzadera TCUE and C2 program (Universidad de Salamanca) (to ASL); the Spanish National Research Council (CSIC) funded by the Junta de Castilla y León and co-financed by the European Regional Development Fund (ERDF “Europe drives our growth)”: Internationalization Project “CL-EI-2021-08-IBFG Unit of Excellence”, Grant (PID2022-138478OA-100) funded by MICIU/AEI/10.13039/501100011033 and, by FEDER, UE (to MGM); Junta de Castilla y León (SA225P23) and Gerencia Regional de Salud (2701/A1/2023) (to AV); and the Plan Especial Grado Medicina (USAL) (to CPM). MGM is a Ramón y Cajal researcher: Grant RYC2021- 033684-I funded by MICIU/AEI/10.13039/501100011033 and, by European Union NextGenerationEU/PRTR.

PDF

4

摘要：

远洋鱼类的视觉系统不断发展，成为研究中枢神经系统再生的有用模型。神经胶质细胞是这一过程的关键，但它们的贡献尚未得到很好的界定。实验利用sox10:tagRFP转基因品系和共聚焦显微镜观察了成年斑马鱼视觉系统中的少突胶质细胞在视神经损伤后6 h，24 h，72h，7 d和14d的再生过程。为了了解这些少突胶质细胞在再生过程中发生的变化，实验使用了Sox2免疫组化技术，这是一种参与少突胶质细胞分化的干细胞标记物。实验还使用 Click-iT™ Plus TUNEL 检测法研究细胞死亡，并使用 BrdU 检测法研究细胞增殖。在视神经挤压前，视网膜、视神经头（ONH）和整个视神经中都有sox10:tagRFP少突胶质细胞。Sox2细胞存在于外周生发区、成熟视网膜和视神经。视神经挤压后，sox10:tagRFP细胞从视神经挤压区消失，表明它们已经死亡，尽管它们不是TUNEL阳性。与此同时，视神经挤压区、视神经头和视网膜周围的Sox2阳性细胞增多。然后，在伤后24 h和14 d之间，视网膜、视神经头和整个视神经都检测到了sox10:tagRFP/Sox2双阳性细胞，伤后72 h时还出现了增殖反应。结果证实，在再生之前可能会出现一个退化过程。首先，围绕退化轴突的sox10:tagRFP少突胶质细胞停止包裹轴突，将其 “髓鞘化少突胶质细胞 ”形态转变为 “非髓鞘化少突胶质细胞 ”形态，然后死亡。然后，视神经和视网膜中残留的少突胶质细胞祖细胞增殖分化，以达到重新髓鞘化的目的。当新的轴突从存活的视网膜神经节细胞中产生时，新的sox10:tagRFP少突胶质细胞从残余的少突胶质细胞祖细胞中产生，以引导、滋养和髓鞘化它们。因此，少突胶质细胞在斑马鱼轴突再生和再髓鞘化过程中发挥着积极作用。

https://orcid.org/0000-0002-6814-0718 (Adrián Santos-Ledo); https://orcid.org/0000-0002-3908-9060 (Marina García-Macia)

关键词: 细胞死亡, 少突胶质细胞, 增殖, 再生, Sox10, Sox2, 视觉系统, 斑马鱼

Abstract: The visual system of teleost fish grows continuously, which is a useful model for studying regeneration of the central nervous system. Glial cells are key for this process, but their contribution is still not well defined. We followed oligodendrocytes in the visual system of adult zebrafish during regeneration of the optic nerve at 6, 24, and 72 hours post-lesion and at 7 and 14 days post-lesion via the sox10:tagRFP transgenic line and confocal microscopy. To understand the changes that these oligodendrocytes undergo during regeneration, we used Sox2 immunohistochemistry, a stem cell marker involved in oligodendrocyte differentiation. We also used the Click-iT™ Plus TUNEL assay to study cell death and a BrdU assay to determine cell proliferation. Before optic nerve crush, sox10:tagRFP oligodendrocytes are located in the retina, in the optic nerve head, and through all the entire optic nerve. Sox2-positive cells are present in the peripheral germinal zone, the mature retina, and the optic nerve. After optic nerve crush, sox10:tagRFP cells disappeared from the optic nerve crush zone, suggesting that they died, although they were not TUNEL positive. Concomitantly, the number of Sox2-positive cells increased around the crushed area, the optic nerve head, and the retina. Then, between 24 hours post-lesion and 14 days post-lesion, double sox10:tagRFP/Sox2-positive cells were detected in the retina, optic nerve head, and whole optic nerve, together with a proliferation response at 72 hours post-lesion. Our results confirm that a degenerating process may occur prior to regeneration. First, sox10:tagRFP oligodendrocytes that surround the degenerated axons stop wrapping them, change their “myelinating oligodendrocyte” morphology to a “nonmyelinating oligodendrocyte” morphology, and die. Then, residual oligodendrocyte progenitor cells in the optic nerve and retina proliferate and differentiate for the purpose of remyelination. As new axons arise from the surviving retinal ganglion cells, new sox10:tagRFP oligodendrocytes arise from residual oligodendrocyte progenitor cells to guide, nourish and myelinate them. Thus, oligodendrocytes play an active role in zebrafish axon regeneration and remyelination.

Key words: cell death, oligodendrocytes, optic nerve, proliferation, regeneration, Sox10, Sox2, visual system, zebrafish