Circadian rHythms and theiR associatiON with myOPIA

Myopia or short-sightedness is a refractive error caused by excessive eyeball elongation, resulting in distant objects appearing blurry. Its global prevalence is increasing rapidly and is estimated to affect half of the global population by 2050. Several recent studies have suggested a link between circadian rhythms and eye development. An analysis at the Estonian Biobank revealed a robust association between myopia and an individual’s sleep timing preference, or chronotype. Individuals with late chronotype were more likely to have myopia, while early chronotype was associated with hyperopia. This project, CHRONOPIA, aims to uncover the underlying mechanisms and directionality of this relationship. It seeks to understand how circadian rhythms influence eye growth and how refractive errors, in turn, impact circadian rhythms. The effect of circadian rhythms on refractive development will be studied in mice by employing various circadian biology paradigms with simultaneous monitoring of refractive development. The impact of refractive errors on circadian rhythms will be evaluated using the mouse model of lens-induced myopia and hyperopia, circadian phenotyping techniques, retinal transcriptomics, and ex vivo assessment of retinal circadian rhythms. Finally, through genome-wide gene-based association studies, this project will analyze the molecular similarities between the mouse model of myopia and human myopia. This provides an opportunity to discover novel genes and pathways associated with human myopia and to determine how well the mouse model of the disease models human myopia on a molecular level. By elucidating the interactions between refractive errors and circadian rhythms, we aspire to contribute valuable insights into the molecular mechanisms that could guide the development of innovative preventive and therapeutic strategies to address the escalating myopia epidemic.