Modern lifestyle changes have contributed to a marked increase in myopia and visual impairments in recent decades. However, the systemic biological effects and underlying mechanisms of prolonged exposure to different artificial light sources remain poorly understood. To address this gap, two-week-old female guinea pigs were randomly assigned to three groups: an indoor natural light (IN) control group, a light-emitting diode (LED) group, and a screen video (SV) group. Animals were maintained under a 12:12-h light-dark cycle (lights on 08:00 h, lights off 20:00 h) for 12 weeks. Ocular axial length, peripheral hormone profiles, and systemic glucose-lipid metabolism were evaluated across the three lighting environments. Compared with the IN group, both the LED and SV groups exhibited significant ocular axial elongation, dysregulated lipid metabolism, and altered endocrine profiles. Retinal expression of melanopsin - the photopigment in intrinsically photosensitive retinal ganglion cells (ipRGCs) that regulates non-image-forming visual functions and circadian photoentrainment - was significantly upregulated in the artificial light groups. Molecular analyses further revealed downregulation of key reproductive and metabolic genes (Gnrh1, Cyp17a1, and Flt4) alongside upregulation of hypothalamic circadian clock genes and Kiss1. These findings suggest that artificial light spectra elevate retinal melanopsin expression, which, combined with altered hypothalamic clock gene activity, disrupts reproductive, and metabolic homeostasis. This work highlights a potential role for melanopsin-mediated non-image-forming pathways in light-induced endocrine and metabolic disorders, warranting further mechanistic investigation.
