中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (5): 795-803.doi: 10.4103/1673-5374.206651

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

斑马鱼视网膜感光细胞缺损再生与行为学变化的联系

  

  • 收稿日期:2017-04-02 出版日期:2017-05-15 发布日期:2017-05-15
  • 基金资助:

    国家自然科学基金（81301080，81671179）；中央高校基础研究基金（63161215）；天津市自然科学基金（15JCYBJC24400, 15JCQNJC10900）

Correlation between photoreceptor injuryregeneration and behavior in a zebrafish model

Ya-jie Wang1, 2, Shi-jiao Cai1, Jian-lin Cui1, Yang Chen1, Xin Tang2, Yu-hao Li1   

  1. 1 Key Laboratory of Tumor Microenviroment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin, China; 2 Cataract Center, Tianjin Eye Hospital, Tianjin, China
  • Received:2017-04-02 Online:2017-05-15 Published:2017-05-15
  • Contact: Yu-hao Li, M.D. or Xin Tang, M.D.,liyuhao@nankai.edu.cn or tangprofessor@aliyun.com.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81301080, 81671179; the Fundamental Research Funds for the Central Universities in China, No. 63161215; the Natural Science Foundation of Tianjin of China, No. 15JCYBJC24400, 15JCQNJC10900.

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摘要：

过强的可见光直接照射眼睛会导致黄斑损伤等日光性视网膜病变，损伤后出现中央暗点、视物变形、视力下降等症状。然而，强光对视网膜损害后在细胞水平的变化目前报道较少。鉴于斑马鱼感光细胞的分布情况及基因表达模式和人类非常相似，并且感光细胞损伤后可诱导干细胞基础上的细胞再生；因此，斑马鱼视网膜被认为是模拟人类感光细胞损伤的理想模型。实验以强光持续照射选择性清除成体斑马鱼视网膜中央部的感光细胞，通过免疫组织化学和原位杂交的方法评估视锥细胞和视杆细胞在光照后1，3，7 d的细胞损伤、增殖及再生情况，并采用黑白箱实验对感光细胞损伤再生过程中斑马鱼的运动能力进行测试。结果表明，在光照损伤后第7天，斑马鱼的视网膜感光细胞可再生，但再生的感光细胞排列紊乱；在感光细胞损伤再生过程中，斑马鱼运动能力降低、趋光性减弱，但运动角速度增加，这些行为学改变在一定程度上与视网膜损伤再生的细胞形态学变化相一致。结果说明，斑马鱼的视网膜有很强的再生能力，其受损的视力及光刺激后所产生的应激反应会共同导致斑马鱼行为的改变。

ORCID：0000-0003-2022-9526(Yu-hao Li);0000-0002-7501-2837(Xin Tang)

关键词: 神经再生, 视神经损伤, 光损伤, 视网膜感光细胞, 细胞增殖, 细胞再生, 黑白箱实验, 行为学, 斑马鱼, 趋光性, 免疫组织化学染色, 原位杂交

Abstract:

Direct exposure to intensive visible light can lead to solar retinopathy, including macular injury. The signs and symptoms include central scotoma, metamorphopsia, and decreased vision. However, there have been few studies examining retinal injury due to intensive light stimulation at the cellular level. Neural network arrangements and gene expression patterns in zebrafish photoreceptors are similar to those observed in humans, and photoreceptor injury in zebrafish can induce stem cell-based cellular regeneration. Therefore, the zebrafish retina is considered a useful model for studying photoreceptor injury in humans. In the current study, the central retinal photoreceptors of zebrafish were selectively ablated by stimulation with high-intensity light. Retinal injury, cell proliferation and regeneration of cones and rods were assessed at 1, 3 and 7 days post lesion with immunohistochemistry and in situ hybridization. Additionally, a light/dark box test was used to assess zebrafish behavior. The results revealed that photoreceptors were regenerated by 7 days after the light-induced injury. However, the regenerated cells showed a disrupted arrangement at the lesion site. During the injury-regeneration process, the zebrafish exhibited reduced locomotor capacity, weakened phototaxis and increased movement angular velocity. These behaviors matched the morphological changes of retinal injury and regeneration in a number of ways. This study demonstrates that the zebrafish retina has a robust capacity for regeneration. Visual impairment and stress responses following high-intensity light stimulation appear to contribute to the alteration of behaviors.

Key words: nerve regeneration, optic nerve injury, light injury, photoreceptor cell, cell proliferation, retinal regeneration, light/dark test, behavior, zebrafish, phototaxis, immunohistochemistry, in situ hybridization, neural regeneration