Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (8): 3863-3869.doi: 10.4103/NRR.NRR-D-25-00168

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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).

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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