中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (4): 922-928.doi: 10.4103/1673-5374.353848

• 原著:视神经损伤修复保护与再生 • 上一篇    

坏死性凋亡在加重眼钝挫伤后视网膜损伤的重要作用

  

  • 出版日期:2023-04-15 发布日期:2022-10-31
  • 基金资助:
    国家自然科学基金项目（81600738）；空军医科大学青年发展项目（21QNPY072）

Necroptosis plays a crucial role in the exacerbation of retinal injury after blunt ocular trauma

Yu Huan1, #, Xiu-Quan Wu1, #, Tao Chen2, 3, #, Ya-Nan Dou1, Bo Jia1, Xin He1, Dong-Yu Wei2, Zhou Fei1, *, Fei Fei4, *   

  1. 1Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi Province, China;  2Center of Clinical Aerospace Medicine, Air Force Medical University, Xi’an, Shaanxi Province, China;  3Department of Aviation Medicine, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi Province, China;  4Department of Ophthalmology, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi Province, China
  • Online:2023-04-15 Published:2022-10-31
  • Contact: Fei Fei, feeplus@163.com; Zhou Fei, feizhou@fmmu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81600738; the Youth Development Project of Air Force Medical University, No. 21QNPY072 (both to FF).

PDF

47

摘要：

眼钝挫伤后视网膜损伤可能直接影响预后，并导致视力丧失。为研究眼钝挫伤后视网膜损伤的病理变化和分子机制，实验建立了自由落体打击比格犬眼钝挫伤模型，以苏木精-伊红染色、免疫荧光染色、western blot和TUNEL法观察损伤后14d内视网膜的变化。结果发现：（1）与对照组相比，眼钝挫伤后14d内，视网膜节细胞的数量随时间逐渐减少，内核层和外核层的厚度也逐渐减少。内核层中双极细胞在损伤后第1天即开始减少，而内核层中的胆碱能细胞和无长突细胞的数量直到第7天才减少，且损伤后视网膜细胞的坏死量随时间增加，也从外核层向内核层发展。（2）视觉电生理学结果表明，视觉障碍从损伤后第1天开始，并随着时间的推移而加重。（3）此外，眼钝挫伤不仅可诱导视网膜Müller细胞的神经再生和胶质增生，还可导致小胶质细胞向视网膜募集和极化为M1表型。（4）这些数据说明，坏死性凋亡在眼钝挫伤后可通过胶质增生和神经炎症加重视网膜损伤中起重要作用，可能给予更多研究者发现与之相关的潜在的治疗策略提供实验数据。

https://orcid.org/0000-0001-6194-5663 (Fei Fei);  https://orcid.org/0000-0003-3276-6345 (Zhou Fei) 

关键词: 眼钝挫伤, 神经胶质增生, 神经炎症, 坏死性凋亡, 视网膜损伤, Müller细胞, M1小胶质细胞, 视网膜神经节细胞, 比格犬, 自由落体打击损伤

Abstract: Retinal injury after blunt ocular trauma may directly affect prognosis and lead to vision loss. To investigate the pathological changes and molecular mechanisms involved in retinal injury after blunt ocular trauma, we established a weight drop injury model of blunt ocular trauma in male Beagle dogs. Hematoxylin-eosin staining, immunofluorescence staining, western blotting, and TUNEL assays were performed to investigate retinal injury within 14 days after blunt ocular trauma. Compared with the control group, the thicknesses of the inner and outer nuclear layers, as well as the number of retinal ganglion cells, gradually decreased within 14 days after injury. The number of bipolar cells in the inner nuclear layer began to decrease 1 day after injury, while the numbers of cholinergic and amacrine cells in the inner nuclear layer did not decrease until 7 days after injury. Moreover, retinal cell necroptosis increased with time after injury; it progressed from the ganglion cell layer to the outer nuclear layer. Visual electrophysiological findings indicated that visual impairment began on the first day after injury and worsened over time. Additionally, blunt ocular trauma induced nerve regeneration and Müller glial hyperplasia; it also resulted in the recruitment of microglia to the retina and polarization of those microglia to the M1 phenotype. These findings suggest that necroptosis plays an important role in exacerbating retinal injury after blunt ocular trauma via gliosis and neuroinflammation. Such a role has important implications for the development of therapeutic strategies.

Key words: Beagle dogs, blunt ocular trauma, gliosis, M1 microglia, Müller cells, necroptosis, neuroinflammation, retinal ganglion cells, retinal injury, weight drop injury