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This study investigates how different lighting cycles affect circadian rhythms and retinal degeneration in rd10 mice.

April 25, 2026Experimental Eye Research0 citationsOpen Access

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

PLPedro LaxUniversity of Alicante MRMateo Ruiz‐ConcaUniversity of Alicante NMNatalia Martínez‐GilUniversity of Alicante

Key Points

This study investigates how different lighting cycles affect circadian rhythms and retinal degeneration in rd10 mice.
Homozygous rd10 mice were exposed to either a 12:12 h light-dark cycle or a 3:3 h light-dark cycle from postnatal day 19 (P19) to P27.
Spontaneous locomotor activity was recorded continuously, and retinal health was assessed using electroretinography and optical coherence tomography (OCT).
Oxidative stress was measured through DHE fluorescence in the retina.
Mice in the 3:3 h light-dark cycle showed significant deterioration in circadian rhythmicity, with reduced circadian amplitude and loss of periodicity.
Retinal responsiveness decreased in the 3:3 h group, with significant differences in b-wave amplitudes compared to the 12:12 group.
DHE fluorescence indicated increased oxidative stress in photoreceptors of mice under the 3:3 h light-dark cycle.

Abstract

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. • Light-dark 3:3 h cycles induce circadian disruption in retinitis pigmentosa mice • Light induced circadian disruption enhances oxidative stress in retinitis pigmentosa • Circadian disruption exacerbates retinal degeneration in the rd10 mouse model of RP Title :

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