Abstract: Photobiomodulation therapy (PBMT) has emerged as a promising non-pharmacological physical intervention for myopia control. However, the optimal irradiation parameters and the underlying mechanisms remain to be further clarified. In this study, a form-deprivation myopia (FDM) mouse model was established, and 650 nm PBMT protocols with different power densities were applied to systematically evaluate the inhibitory effect of PBMT on myopia-associated axial elongation. Changes in dopamine (DA) and nitric oxide (NO) levels in the retinal were quantified, and the efficacy and safety of long-term PBMT were further assessed. In addition, ex vivo cell experiments were performed to investigate downstream molecular responses to DA. The results showed that PBMT significantly suppressed abnormal axial elongation in FDM mice (P<0.05), with the most prominent effect observed at a power density of 0.25 mW/cm2. PBMT also markedly increased DA and NO secretion in the retinal (P<0.05) in a dose-dependent manner. Long-term PBMT stably inhibited axial elongation during myopia development without significantly affecting axial length in normal mice, suggesting a favorable safety profile. Furthermore, DA upregulated cellular FBJ osteosarcoma oncogene (c-Fos) expression and promoted tissue inhibitor of metalloproteinases (TIMP2) gene expression in retinal pigment epithelial cells, and these effects were attenuated by D1R inhibition, indicating that the DA-D1R-mediated c-Fos/TIMP2 pathway may contribute to PBMT-induced suppression of axial elongation. Collectively, these findings demonstrate that PBMT effectively alleviates myopia progression in FDM mice, potentially by activating retinal DA/NO signaling and modulating molecular networks associated with tissue remodeling, thereby providing experimental evidence for parameter optimization and mechanistic exploration of red-light-based myopia interventions.
Key words: photobiomodulation therapy; dopamine; myopia; sclera; retinal pigment epithelium
（Acta Laser Biology Sinica, 2026, 35(2): 185-192）