IOVS 2027

Background: Amblyopia is the most common childhood neurodevelopmental visual disorder, arising from impaired synaptic plasticity in the primary visual cortex (V1) due to abnormal visual experience during the critical period. Electroacupuncture (EA) has been clinically applied as a non-invasive adjunctive therapy for amblyopia, but whether its therapeutic effects depend on the Wnt/β-catenin pathway remains unknown.

Methods: Using monocular deprivation (MD) rats, we integrated transcriptome sequencing, weighted gene co-expression network analysis (WGCNA), and multiple machine-learning algorithms to screen core pathways and hub genes associated with V1 synaptic plasticity after MD. Two independent batches of animal experiments were designed. Batch 1 (NC, MD, EA) examined EA effects on visual function and Wnt pathway protein expression. Batch 2 (NC, MD, MD+DMSO, EA, EA+XAV, MD+XAV) tested whether EA effects depend on Wnt/β-catenin pathway integrity using XAV-939, a selective tankyrase inhibitor that promotes β-catenin degradation, with verification by Western blotting, qPCR, immunofluorescence, and transmission electron microscopy (TEM).

Results: Canonical Wnt signaling was significantly suppressed in MD V1, and Rcn3, Htr1a, Tbxt, Wnt3, and Ctnnb1 were identified as hub genes. EA significantly restored the fVEP C/I ratio in MD rats. MD decreased Wnt3, β-catenin, BDNF, and PSD-95 expression, reduced synaptic density, shortened synaptic length, and thinned PSD, whereas EA ameliorated these changes. XAV-939 attenuated the EA-induced improvements in β-catenin nuclear translocation, BDNF/PSD-95 expression, and synaptic ultrastructure.

Conclusions: EA improves visual function by activating the Wnt/β-catenin pathway, upregulating BDNF and PSD-95, and repairing MD-induced synaptic ultrastructural damage. These findings provide preclinical mechanistic support for EA as an adjunctive rehabilitation strategy for amblyopia.

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