New perspectives in amblyopia therapy on adults: a critical role for the excitatory/inhibitory balance

Abstract

Amblyopia is the most common form of impairment of visual function affecting one eye, with a prevalence of about 1-5% of the total world population. This pathology is caused by early abnormal visual experience with a functional imbalance between the two eyes owing to anisometropia, strabismus, or congenital cataract, resulting in a dramatic loss of visual acuity in an apparently healthy eye and various other perceptual abnormalities, including deficits in contrast sensitivity and in stereopsis. It is currently accepted that, due to a lack of sufficient plasticity within the brain, amblyopia is untreatable in adulthood. However, recent results obtained both in clinical trials and in animal models have challenged this traditional view, unmasking a previously unsuspected potential for promoting recovery after the end of the critical period for visual cortex plasticity. These studies point toward the intracortical inhibitory transmission as a crucial brake for therapeutic rehabilitation and recovery from amblyopia in the adult brain.

Keywords: GABAergic inhibition; amblyopia; environmental enrichment; fluoxetine; neural plasticity; perceptual learning.

Figure 1

Pharmacological and environmental therapeutic strategies for amblyopia in adulthood. Recent data have documented a previously unsuspected high potential of neuronal plasticity in the adult visual cortex. In animal models, plasticity can be elicited either by pharmacological treatment with chronic administration of antidepressants (fluoxetine), valproic acid (an inhibitor of histone deacetylases), or chondroitinase ABC (which degrades the extracellular matrix chondroitin sulfate proteoglycans), and by exposure to environmental enrichment, housing in complete darkness, or caloric restriction. In humans, emerging clinical studies point to active visual stimulation obtained with perceptual learning or playing video games as a promising strategy for treating amblyopia in adulthood. An increased ratio between excitation and inhibition owing to a reduced intracortical inhibitory tone is thought to be a central hub triggering plasticity in the adult visual cortex.