中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (8): 3863-3869.doi: 10.4103/NRR.NRR-D-25-00168

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

视网膜色素变性诱发中枢神经系统的退行性病理变化

  

  • 出版日期:2026-08-18 发布日期:2026-04-28

Retinitis pigmentosa elicits neurodegeneration within the visual pathway in REEP6 knockout mice

Yin Yang1, 2, 3, #, Maoxia Lv1, #, Binbin Qiao1, 4, #, Zhengjiang Yang2, Houbin Zhang1, 2, 3, Zhengzheng Wu1, 2, 3, Yang Xia2, *, Dezhong Yao1, 2, 3, *, Ke Chen1, 2, 3, *   

  1. 1Department of Ophthalmology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, China; 
    2Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, China; 
    3Research Unit for Blindness Prevention, Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, Sichuan Province, China; 
    4Department of Ophthalmology, Chongzhou People’s Hospital, Chengdu, Sichuan Province, China
  • Online:2026-08-18 Published:2026-04-28
  • Contact: Yang Xia, PhD, xiayang@uestc.edu.cn; Dezhong Yao, PhD, dyao@uestc.edu.cn; Ke Chen, PhD, chenke0703@uestc.edu.cn.
  • Supported by:
    This study was supported by STI 2030-Major Projects, No. 2022ZD0208503 (to DY); the Fund of Chinese Academy of Science (“Xi Bu Zhi Guang” Project) (to YY); and the Sichuan Science and Technology Program, No. 2023YFS0312 (to YY).

摘要:

尽管中枢神经系统退行性疾病常与年龄相关性黄斑变性和青光眼相关,但其与视网膜色素变性(一种由杆状光感受器中表达的受体表达增强蛋白6(REEP6)异构体引起的视网膜退行性疾病)的关系鲜少被研究。实验采用REEP6基因敲除小鼠模型(REEP6−/−)及其对照组(REEP6+/+),在视网膜色素变性进展过程中的3个特定时间点(1,6和10个月)对视觉通路的神经退行性病理变化及初级视觉皮层的神经活动进行研究。自1月龄起,视网膜和初级视觉皮层区域均观察到小胶质细胞活化,但侧膝状核在任何时间点均未检测到此类活化。在REEP6−/−小鼠的初级视觉皮层区域,6个月和10个月时观察到小胶质细胞活化的增加,这与这些时间点磷酸化tau(p-Tau)水平的升高相一致。在6和10个月时,REEP6−/−小鼠的初级视觉皮层神经元对条纹刺激的反应减弱,与对照组相比自发活动增加。研究发现,视网膜色素变性会在小鼠视觉通路中诱发神经退行性病理变化,尤其在初级视觉皮层区域,这表明眼部疾病对中枢神经系统退化具有显著贡献。


https://orcid.org/0009-0009-7901-1629 (Yang Xia);

https://orcid.org/0000-0002-8042-879X (Dezhong Yao); 

https://orcid.org/0000-0003-2209-1452 (Ke Chen)

关键词: 视网膜色素变性, 受体表达增强蛋白6, 神经退行性变, 视觉通路, 细胞外电生理学, 光感受器变性, 初级视觉皮层, 神经退行性变, 神经再生

Abstract:

While degenerative diseases of the central nervous system are commonly linked to age-related macular degeneration and glaucoma, they have also been infrequently associated with retinitis pigmentosa, a condition defined by retinal degeneration that can be caused by an isoform of receptor expression enhancing protein 6 (REEP6) expressed in rod photoreceptors. In this study, we used REEP6 knockout mice (REEP6–/–) and wild-type mice (REEP6+/+) to examine neurodegenerative pathology within the visual pathways and neural activity in the primary visual cortex (V1) at three specific time points (1, 6, and 10 months) during retinitis pigmentosa progression. Microglial activation was observed in both the retina and the primary visual cortex starting at 1 month of age, but no such activation was detected in the lateral geniculate nucleus at any time point. Not only was increased microglial activation observed at 6 and 10 months within the primary visual cortex of REEP6–/– mice, but also coinciding with elevated levels of phosphorylated Tau expression. At 6 and 10 months of age, primary visual cortex neurons in REEP6–/– mice exhibited reduced responses to grating stimuli and increased spontaneous activity compared with neurons in the primary visual cortex of mice in the control group. Our findings show that retinitis pigmentosa induces neurodegenerative pathology within the visual pathway of mice, particularly in the primary visual cortex, suggesting that ocular disease contributes substantially to central nervous system degeneration. It may provide new clues for the selection of treatment opportunities and the development of therapeutic measures for the subsequent treatment of retinitis pigmentosa or even other retinal degenerative diseases.

Key words: microglial activation, nerve regeneration, neurodegeneration, phosphorylated Tau, photoreceptor degeneration, primary visual cortex (V1), REEP6, retinitis pigmentosa, rod photoreceptors, visual pathway