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Deepa Mathew, Ashay D Bhatwadekar; Circadian Rhythm Disruption Results in Photoreceptor Degeneration and Visual Dysfunction. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2711.
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© ARVO (1962-2015); The Authors (2016-present)
Circadian rhythm disruption (CRD) is associated with metabolic and neurodegenerative diseases. However, its effect on vision is poorly understood. The aim of the study was to assess the impact of CRD on retinal morphology, physiology and vision, using an environmental CRD paradigm.
C57BL/6J male mice were housed either in 10 hr light: 10 hr dark cycle (T20) for CRD or in 12 hr light: 12 hr dark cycle (T24) as control and their wheel-running activity was continuously monitored to assess the circadian behavior. The retinal function and visual acuity were assessed with electroretinogram (ERG) and optomotor response, between 10-14 weeks of CRD. Retinal morphology was evaluated by optical coherence tomography (OCT) in vivo and by immunohistochemistry. The total proteome analysis was performed on isolated retina to study alterations at the molecular level.
The T20 mice exhibited three different circadian behaviors; entrained, ‘free-running’ and ‘zigzagging’. The entrained group had significantly reduced scotopic ERG a-wave and b-wave amplitudes, lower visual acuity and reduced retinal thickness. The ‘free-running’ and ‘zigzagging’ behavior groups exhibited reduced visual acuity and retinal thickness while their scotopic ERG amplitudes were not affected. Immunohistochemistry revealed a significantly thinner photoreceptor layer in the entrained mice. The total proteome analysis revealed several differentially expressed proteins related to synaptic plasticity, retinal ganglion cell survival and photoreceptor function including rhodopsin.
Our results demonstrate that CRD resulted in photoreceptor degeneration and visual dysfunction. We uniquely show the effect of circadian behavior on retinal physiology. Our data has broader implications in understanding and mitigating the impact of CRD, as in shift work and jetlag, on vision health.
This is a 2020 ARVO Annual Meeting abstract.
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