Circadian Rhythm Disruption Results in Visual Dysfunction

Abstract Circadian rhythm disruption (CRD) contributes to the development of multiple metabolic and neurodegenerative diseases. However, its effect on vision is not understood. We evaluated the impact of CRD on retinal morphology, physiology, and vision after housing mice in a disruption inducing shorter light/dark cycle (L10:D10). Interestingly, the mice under L10:D10 exhibited three different entrainment behaviors; ‘entrained’, ‘freerunning’, and ‘zigzagging.’ These behavior groups under CRD exhibited reduced visual acuity, retinal thinning, and a decrease in the number of rod photoreceptors. Intriguingly, the electroretinogram response was decreased only in the mice exhibiting ‘entrained’ behavior. The retinal proteome showed distinct changes with each entrainment behavior. These results demonstrate that CRD leads to photoreceptor degeneration and visual dysfunction. We uniquely show the effect of entrainment behavior on retinal protein composition and physiology. Our data has broader implications in understanding and mitigating the effect of CRD on vision health. Significance StatementArtificial light is increasingly in use for the past 70 years. The aberrant light exposure and round-the-clock nature of work lead to the disruption of a biological clock. The mammalian retina possesses an autonomous clock that could reset with light exposure. Yet, the effect of altered light exposure on vision is not studied. Here, we report visual dysfunction after exposure to a circadian disrupting altered light/dark cycle. We also report behavior dependent changes in retinal protein composition and function. Our data provide evidence for the negative impact of CRD on vision and its potential role in retinal diseases’ etiology.