Target epigenetics mechanism to prevent synaptic dysfunction of adult amblyopia

Amblyopia is a neurodevelopmental disorder, and there are no effective treatment methods for adult amblyopia patients due to the decline in synaptic plasticity in visual cortex. Enriched environment (EE) has been shown to enhance synaptic plasticity, which is mediated, at least in part, by epigenetic mechanisms involving histone acetylation. This study aims to investigate whether histone deacetylase (HDAC) inhibitors can replicate the effects of EE on visual cortical plasticity, thereby offering novel therapeutic insights for adult amblyopia. First, we established adult amblyopia mice model, which were then randomized into five groups: untreated amblyopia, standard housing, EE, vehicle, trichostatin A (TSA) groups, with normal mice serving as controls. To evaluate synaptic plasticity in visual cortex, we measured synaptic marker VGLUT2, synaptic ultrastructure and long-term potentiation (LTP). Additionally, biochemical analyses were conducted to measure alterations of HDACs associated with synaptic integrity. Our findings revealed that EE enhanced synaptic plasticity in visual cortex of adult amblyopia mice and was associated with reduced HDAC3 expression. Similarly, the broad HDAC inhibitor TSA, improved synaptic ultrastructure, increased VGLUT2 expression, and potentiated LTP, functionally resembling several key effects of EE. Importantly, TSA targets multiple HDAC isoforms, and the observed reduction in HDAC3 levels is correlated with, but does not establish, a causal role for HDAC3. These results indicate that broad HDAC inhibition can mimic EE-induced plasticity in adult amblyopia, while highlighting the need for selective HDAC3-targeted approaches to determine mechanistic specificity. Overall, our study provides a foundation for developing epigenetic-based strategies to enhance adult visual cortical plasticity.