Circadian rhythm disruption induces myopia in mice.

Abstract

Emerging evidence suggests a link between circadian rhythm and myopia, with studies showing that retinal-specific knockout of the clock gene Bmal1 induces myopia in mice. This study aims to elucidate the relationship between circadian rhythm disruption (CRD) and myopia, and to investigate the potential mechanisms underlying CRD-mediated myopia development. Three-week-old C57BL/6J mice were entrained to a 12 h light/12 h dark (12L/12D) photoperiod for one week. Mice were then randomly assigned to the 12L/12D control group and the CRD groups. CRD groups were divided into two subgroups: Chronic jet lag (light cycle conditions with an 8 h dark advance every 2-3 days, CJL) and Irregular (light cycle conditions alternating among 16L/8D, 8L/16D and 12L/12D). Refraction and axial length (AL) were measured. Further analysis of pathogenic mechanisms was conducted using RNA sequencing. CRD shifted refraction (control vs Irregular: two weeks: 2.61&#xa0;&#xb1;&#xa0;0.91 D vs -3.97&#xa0;&#xb1;&#xa0;1.91 D, P&#xa0;=&#xa0;0.01; four weeks: 1.64&#xa0;&#xb1;&#xa0;0.72 D vs -5.3&#xa0;&#xb1;&#xa0;1.09 D, P&#xa0;<&#xa0;0.0001; control vs CJL: two weeks: 2.61&#xa0;&#xb1;&#xa0;0.91 D vs -3.93&#xa0;&#xb1;&#xa0;1.6 D, P&#xa0;=&#xa0;0.004; four weeks: 1.64&#xa0;&#xb1;&#xa0;0.72 D vs -6.2&#xa0;&#xb1;&#xa0;1.36 D, P&#xa0;<&#xa0;0.001) and increased AL (four weeks: control vs Irregular, 3.318&#xa0;&#xb1;&#xa0;0.01&#xa0;mm vs 3.363&#xa0;&#xb1;&#xa0;0.008&#xa0;mm, P&#xa0;=&#xa0;0.001; control vs CJL, 3.318&#xa0;&#xb1;&#xa0;0.01&#xa0;mm vs 3.359&#xa0;&#xb1;&#xa0;0.008&#xa0;mm, P&#xa0;=&#xa0;0.004) towards myopia. RNA-sequencing revealed significant enrichment of genes involved in neurotransmitter signaling pathways, including GABAergic synapses, glutamatergic synapses, dopaminergic synapses and synaptic vesicle cycles. This study indicates that circadian rhythm disruption can induce myopia in mice, with RNA-sequencing supporting the potential role of neurotransmitter signaling pathways.