Sustained activation of Wnt/β-catenin signaling in the retina of form-deprived myopic chicks

Form-deprivation myopia (FDM) in chicks is one of the key models for studying myopia development. The specific molecular events and activation dynamics within the retina during early FDM stage in chicks remain unclear. Retinal transcriptome datasets (GSE161497, GSE227724) were analyzed using DESeq2 and edgeR to identify differentially expressed genes (DEGs). Protein-protein interaction networks were constructed and visualized, with hub genes identified via the Maximal Clique Centrality algorithm. Functional enrichment was analyzed. Western Blot was used to validate β-catenin and phospho-β-catenin protein expression in control, FDM 1d, and FDM 5d chick retinas. Analysis revealed 36 common DEGs between DESeq2 and edgeR. PPI network analysis identified CTNNB1 (β-catenin), GNAQ, and TSHR as the top three hub genes. Western Blot demonstrated significant and sustained upregulation of both total β-catenin and phospho-β-catenin protein levels in FDM 1d and FDM 5d retinas compared to controls, with peak expression at FDM 5d within observed time. This study provides evidence of sustained activation of the Wnt/β-catenin signaling pathway specifically within the chick retina during early FDM development, highlighted by CTNNB1 as a top hub gene and confirmed by progressive increases in both total and activated β-catenin protein. This suggests a potentially conserved role for retinal Wnt/β-catenin signaling in myopia pathogenesis.