从损伤到恢复：斑马鱼视神经切断后视觉通路自发性结构与功能再生的时空动态研究
Year: 2025
Type: article
Abstract: In adult mammals, optic nerve injury leads to irreversible vision loss due to its extremely limited regenerative capacity. In contrast, adult zebrafish possess a robust capacity for spontaneous visual system regeneration, although the spatiotemporal coordination of recovery across the retina, optic nerve, and brain remains poorly understood. In the present study, the regenerative dynamics following optic nerve transection were systematically characterized in adult zebrafish over a 5 week period using hematoxylin-eosin staining, immunohistochemistry, transmission electron microscopy, single-cell RNA sequencing, and optokinetic response (OKR) behavioral assessments. At 1 week post-injury (1 wpi), retinal ganglion cell depletion was evident but showed significant recovery by 2 wpi. Concurrently, the injured optic nerve displayed a marked increase in diameter and cell number at 2 wpi, including widespread expression of proliferating cell nuclear antigen, consistent with heightened proliferative activity. Single-cell transcriptomic profiling at 2 wpi revealed five principal cell populations: fibroblasts, mural cells, immune cells, mature oligodendrocytes, and myelin-forming oligodendrocytes. By 4-5 wpi, remyelination within the optic nerve and re-establishment of synaptic architecture in the optic tectum were strongly correlated with functional restoration of OKR behavior. These findings provide a comprehensive spatiotemporal framework of visual pathway regeneration in zebrafish, establishing a valuable model for elucidating conserved mechanisms of neural repair with translational potential for human vision restoration.
Source: 动物学研究
Authors: Shen Bao-Guo, 温州医科大学附属眼视光医院, 眼健康国家重点实验室, 浙江 温州 325027, 中国, Wen Yuan, Lu Sheng-Jian, Wei Hong-Yuan, Huang Shu-Rui, Zhou Guang-Ming, Yan Wen-Tao, Wu Wen-Can, Zhang Yi-Kui, 温州医科大学附属眼视光医院, 浙江省视觉通路重建关键技术重点实验室, 浙江 温州 325027, 中国, 温州医科大学附属眼视光医院, 国家眼病临床医学研究中心, 浙江 温州 325027, 中国, 瓯江实验室(再生调控与眼脑健康浙江省实验室), 浙江 温州 325027, 中国
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4411362038