Presentation Title: Circadian Rhythm Disruption Results in Visual Dysfunction

Author Name(s): Deepa Mathew and Ashay D Bhatwadekar

Author Department and School Affiliation: Department of Ophthalmology, Indiana University School of Medicine, Indianapolis. IN 46202

Abstract: Circadian rhythm disruption (CRD) is associated with metabolic and neurodegenerative diseases. However, its effect on vision is poorly understood. The study aimed to assess the impact of CRD on retinal morphology, physiology, and vision, by exposing the mice to a shorter light-dark cycle (L10:D10) for 10 weeks. The L10:D10 mice exhibited three different circadian wheel running behaviors; ‘entrained’, ‘free-running’ and ‘zigzagging’. At the end of 10 weeks, all L10:D10 behavioral groups exhibited reduced visual acuity and retinal thickness, and lesser number of photoreceptor cells. The entrained group had significantly reduced scotopic ERG a-wave and b-wave amplitudes, while the ‘free-running’ and ‘zigzagging’ groups showed normal ERG response. All L10:D10 behavioral groups exhibited specific differential retinal proteome and the entrained group had protein expression changes associated with retinal degeneration. Our results demonstrate that CRD resulted in photoreceptor degeneration and visual dysfunction. Our data uniquely show different circadian behaviors in response to L10:D10 cycle, and their specific effects on retinal physiology. Our data have broader implications in understanding the impact of circadian rhythm disruption on vision health, and possibly mitigating those impacts by behavior modifications.