Repeated low-level red light modulates retinal metabolic alterations in lens-induced myopic chicks.

Abstract

BACKGROUND: Repeated low-level red-light (RLRL) therapy effectively controls myopia, yet its retinal metabolic mechanisms remain elusive. This study aimed to elucidate RLRL-induced metabolic alterations in a lens-induced myopia (LIM) chick model. METHODS: Seven-day-old chicks were randomized into three groups (n = 7 each): normal control (NC), LIM (monocular -10 D lens wear), and LIM + RL (LIM with red-light intervention). The LIM + RL group received 650 nm red light (5 mW cm, 3 min twice daily) for 7 days. Ocular biometry, choroidal thickness, and retinal safety were assessed. Retinal tissues were harvested for untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics, followed by multivariate analysis, pathway enrichment, validation of selected metabolites, and qPCR analysis of pathway-related genes. RESULTS: Red light (RL) reduced myopic shift (-3.82 ± 0.8 D vs -7.75 ± 1.2 D, p = 0.0003) and axial elongation (0.508 ± 0.04 mm vs 0.644 ± 0.03 mm, p = 0.0022), corresponding to 50.6% and 43.3% reduction, respectively. Structurally, RLRL inhibited myopia-associated choroidal thinning without detectable structural retinal damage. Metabolomic profiling revealed that RLRL reversed widespread LIM-induced dysregulation in amino acid and lipid metabolism. Specifically, RLRL upregulated metabolites associated with neuroprotection (N-acetylaspartylglutamate) and visual function (retinene), while downregulating markers linked to inflammation (arachidonic acid) and vascular dysregulation (asymmetric dimethylarginine). qPCR validation further showed that PTGS2 and IL-6 were increased in LIM retinas and reduced after RLRL treatment, whereas NOS3 showed the opposite trend. CONCLUSIONS: RLRL effectively retards myopia progression in chicks by modulating specific retinal metabolic profiles. The protective mechanism involves enhancing mitochondrial energy metabolism, suppressing pro-inflammation lipid pathways, and restoring nitric oxide signaling to preserve choroidal thickness, providing a metabolic basis for RLRL's safety and efficacy.