Environmental Enrichment Enhances Visual Function in Adult Amblyopia: Association With miR-132/HDAC3 Regulation

Amblyopia is a neurodevelopmental disorder for which effective treatments in adults are limited due to reduced cortical plasticity. Environmental enrichment (EE) can partially restore this plasticity, but the underlying molecular mechanisms remain unclear. This study investigated whether the miR-132/HDAC3 pathway is associated with EE-induced visual recovery in adult amblyopic mice. An adult amblyopia model (n = 64) was established via monocular deprivation (MD). Amblyopic mice were assigned to untreated, standard housing (SH), or EE groups, with normal mice as controls. Visual function was assessed using flash visual evoked potentials (fVEP), and molecular analyses of miR-132 and HDAC3 in the primary visual cortex (V1) were performed. In vitro studies included a dual-luciferase assay to verify miR-132-HDAC3 targeting and evaluated the effects of miR-132/HDAC3 overexpression on cortical neurons. Compared to SH, EE-reared amblyopic mice showed (1) increased N1-P2 wave amplitude in fVEP and (2) upregulated miR-132 and downregulated HDAC3 in V1. In vitro, HDAC3 was confirmed as a direct miR-132 target, and miR-132 overexpression suppressed HDAC3 while promoting structural remodeling in visual cortical neurons. These findings suggest that the miR-132/HDAC3 pathway potentially contributes to EE-induced visual restoration in adult amblyopia.