Dim light at night induces cardiac injury in zebrafish embryos via disrupted chloride homeostasis

Summary Artificial light at night (ALAN) is an escalating environmental stressor linked to cardiovascular disease, yet its underlying mechanisms remain poorly understood. Here, we investigate the molecular basis of this pathology using zebrafish embryos for mechanistic discovery and murine models for translational validation under a chronic dim- light- at -night (dLAN) paradigm. dLAN exposure induced cardiac injury characterized by pericardial edema and hemodynamic impairment. Transcriptomic profiling revealed dysregulation of inflammatory and oxidative stress pathways, accompanied by marked suppression of the calcium-activated chloride channel accessory protein zclca1. Genetic knockdown of zclca1 recapitulated core dLAN pathologies, while pharmacological intervention with the chloride-modulating diuretic bumetanide reversed cardiac dysfunction in both species. These findings identify a conserved "dLAN-CLCA-chloride-cardiac injury" axis, wherein light pollution disrupts chloride homeostasis to drive cardiac pathology, suggesting that chloride modulation may represent a potential therapeutic strategy for mitigating light pollution-induced cardiovascular injury.