Multi-genomics data mining identified critical transcription factors and immune response pathways in traumatic optic nerve injury and retinal injury.

BACKGROUND: Traumatic optic nerve and retinal injuries can lead to severe visual impairment, with undetermined underlying molecular mechanism and few reliable molecular biomarkers. This study aims to identify dysregulated genes and signaling pathways potentially involved in these injuries. METHODS: We first identified differentially expressed genes (DEGs) and their enriched functions using two time-course gene expression profile datasets after retinal injury of rats. The hub genes were then obtained from DEGs by protein-protein interaction network, and then assessed by receiver operating characteristic curve analysis to check their diagnostic potential in experimental datasets. The potential miRNAs and transcriptional factors (TFs) of hub genes were also investigated. RESULTS: We identified 312 and 262 DEGs from the two datasets, respectively, with 31 overlapped up DEGs in injury group. These co-up DEGs were highly enriched in immune response-associated pathways and visual system development pathways, including the pivotal JAK-STAT signaling pathway. We then identified 7 hub genes, of which six (Aif1, Cntf, Gfap, Lcn2, Stat1, and Stat3) were validated to be associated with diagnostic relevance in experimental datasets. We predicted 54 miRNAs and 25 TFs participating in the regulatory network of hub genes. Finally, we identified that STAT1 and STAT3 were potential transcriptional regulators in hub genes. CONCLUSION: We identified six critical hub genes and potential regulators that may participate in traumatic optic nerve injury, extending the underlying mechanisms of retinal injury.