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

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.