Controlled Ultraviolet B exposure attenuates form-deprivation myopia by restoring an Egr1-centred retinal transcriptional network

Background Epidemiological studies suggest an inverse association between ultraviolet B (UVB) exposure and myopia. However, whether UVB directly suppresses myopia and the underlying molecular mechanisms remain unclear. We therefore investigated the effects of controlled UVB exposure on form-deprivation myopia (FDM) in mice and characterized the associated retinal transcriptional responses. Methods A modified monocular FDM model was established in mice. Animals were divided into three groups: normal control (NC), form-deprived (FD), and UVB-treated form-deprived (FU) groups. Refractive error and ocular biometric parameters were assessed after 3 weeks. Retinal transcriptomes were analyzed to identify UVB-responsive genes and their regulatory networks. The Egr1-associated transcriptional program was further evaluated using independent retinal transcriptomic and single-cell RNA sequencing datasets. Results Form deprivation induced a significant myopic shift and axial elongation, both of which were substantially attenuated by controlled UVB exposure without detectable ocular structural abnormalities. Transcriptomic analysis identified 98 genes whose form deprivation-induced expression changes were reversed by UVB. Network analysis revealed an Egr1-centered module enriched in immediate-early response and stress-responsive genes. This transcriptional program was independently supported by an Egr1 knockout retinal dataset and exhibited developmental stage-dependent enrichment. Gene set analyses linked the Egr1-associated program to cellular stress responses and cilium- and microtubule-related processes. Single-cell analysis showed that this program was distributed across multiple retinal cell populations, particularly microglia, photoreceptors, and Müller glia. Co-expression analysis identified a retinal module associated with myopia severity and inversely related to UVB exposure. Predicted transcriptional regulators and drug-gene interactions further highlighted potential upstream regulatory and pharmacological connections within the Egr1-centered network. Conclusions Controlled UVB exposure attenuates experimental myopia and is associated with coordinated remodeling of the retinal transcriptional landscape. An Egr1-centered regulatory program may contribute to the retinal response to UVB and its anti-myopic effects. These findings provide a mechanistic framework for evaluating controlled UVB exposure as a potential light-based intervention strategy for myopia.