Light-at-night exposure drives myopia via melanopsin signalling.

Abstract

Myopia poses a growing global public health challenge, with its underlying mechanisms not yet fully understood. While insufficient daytime light exposure is a recognized protective factor, the role of nighttime light exposure remains contentious. Through a murine model, we uncover a novel melanopsin-dependent pathway by which light-at-night (LAN) exposure disrupts the expression of core circadian clock genes (including Arntl, Cry1, Per1, and Per2) and downregulates melanopsin expression in intrinsically photosensitive retinal ganglion cells (ipRGCs). These alterations are associated with axial elongation. Crucially, melanopsin-knockout mice exhibit resistance to myopic changes induced by LAN, indicating that melanopsin-dependent pathways mediate ocular growth responses. Supporting these experimental findings, our epidemiological analysis demonstrates that LAN exposure significantly increases the risk of incident myopia onset in humans. Together, these results establish a functional link between environmental light exposure and the molecular pathogenesis of myopia, identifying LAN as a modifiable risk factor for myopia. Our study provides important insights into the light-mediated myopia development and suggests melanopsin signaling as a potential target for preventive and therapeutic strategies.