Circadian disruption exacerbates oxidative stress and degeneration in the rd10 mouse model of retinitis pigmentosa

Apr 25, 2026Experimental eye research

Disrupted daily rhythms increase cell damage and vision loss in a mouse model of retinitis pigmentosa

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Abstract

Disruption of lighting conditions in mice led to significant deterioration in circadian rhythmicity and retinal health.

Mice exposed to an ultradian 3:3 hour light-dark cycle demonstrated reduced circadian rhythmicity, characterized by diminished amplitude and loss of periodicity.
Retinal responsiveness, measured by b-wave amplitudes, significantly decreased in mice under the ultradian lighting conditions compared to those in a standard 12:12 hour cycle.
Mean retinal thickness was lower in mice subjected to the ultradian lighting, indicating retinal degeneration.
Increased oxidative stress was observed in photoreceptors of mice under the ultradian cycle, as evidenced by higher levels of DHE fluorescence.

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Eye disorders and vision loss have been associated with circadian misalignment and disruption. Nevertheless, growing evidence supports a bidirectional interaction between circadian dysfunction and neurodegeneration, leading to the proposal of circadian disruption as a significant contributing factor to neurodegenerative disorders. This study aimed to assess the impact of disrupting lighting conditions on the circadian rhythmicity and the retinal degenerative process in retinitis pigmentosa mice. Homozygous rd10 mice were maintained under a conventional 12:12 h LD cycle or under an ultradian 3:3 h LD cycle from P19 to P27. Spontaneous locomotor activity was continuously recorded during this period. At P27, retinal responsiveness was assessed by electroretinography, retinal thickness was measured by OCT, and the oxidative stress of the retina was evaluated. Locomotor activity recordings showed deterioration in the circadian rhythmicity of LD 3:3 mice, with small circadian amplitude, low phase homogeneity and loss of circadian periodicity. Besides, retinal responsiveness decreased in LD 3:3 mice, with significant differences between the two groups for b-wave amplitudes. Mean retinal thickness also decreased in LD 3:3 mice. Finally, LD 3:3 mice showed increased levels of DHE fluorescence at the photoreceptor plane, indicating increased oxidative stress. This study provides evidence that exposure to LD 3:3 cycles induces circadian disruption, enhances oxidative stress in photoreceptors and exacerbates retinal degeneration in retinitis pigmentosa mice.

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Circadian disruption exacerbates oxidative stress and degeneration in the rd10 mouse model of retinitis pigmentosa

Abstract

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