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

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.