Comparative Neuroplasticity in Frontal- and Lateral-Eyed Mammals With Induced-Binocular Vision Dysfunction: Insights From Monocular Deprivation Models.

Visual cortical plasticity during early postnatal life is profoundly shaped by species-specific ocular anatomy and ecological demands. This review synthesizes comparative evidence on how monocular deprivation (MD)-a classical model of amblyopia-affects visual system development in frontal- versus lateral-eyed mammals. Frontal-eyed species, including cats and primates, exhibit extensive binocular field overlaps and columnar architecture in the primary visual cortex (V1), making them highly susceptible to MD-induced shifts in ocular dominance and synaptic remodeling. In contrast, lateral-eyed species such as rodents and ungulates possess limited binocular overlaps and lack well-defined ocular dominance columns yet still demonstrate significant MD-induced plasticity involving callosal reorganization, glial activation, and extracellular matrix remodeling. We examine shared and divergent cellular mechanisms underpinning these responses, including the role of parvalbumin-expressing interneurons, perineuronal nets, and neuromodulators like BDNF and NRG1. Rodent models support the notion that even in the absence of classical columnar organization, lateral-eyed species can undergo region-specific structural remodeling in V1 following MD. These distinctions underscore how binocular integration circuits are fine-tuned through extended critical periods in frontal-eyed species, whereas plasticity in lateral-eyed species is more diffusely distributed. The integration of cross-species data revealed conserved principles of visual cortical plasticity and identified mechanisms potentially targetable for amblyopia therapy. Understanding the ecological and anatomical context of plasticity allows for a more accurate interpretation of animal models and supports the development of precision strategies for visual rehabilitation. This comparative framework expands the scope of amblyopia research and offers new avenues for translational interventions.