Metaplasticity: a key to visual recovery from amblyopia in adulthood?

Abstract

We examine the development of amblyopia and the effectiveness of conventional and emerging therapies through the lens of the Bienenstock, Cooper, and Munro (BCM) theory of synaptic modification. The BCM theory posits metaplastic adjustment in the threshold for synaptic potentiation, governed by prior neuronal activity. Viewing established clinical principles of amblyopia treatment from the perspective of the BCM theory, occlusion, blur, or release of interocular suppression reduce visual cortical activity in the amblyopic state to lower the modification threshold and enable amblyopic eye strengthening. Although efficacy of these treatment approaches declines with age, significant loss of vision in the fellow eye by damage or disease can trigger visual acuity improvements in the amblyopic eye of adults. Likewise, reversible retinal inactivation stimulates recovery of amblyopic eye visual function in adult mice and cats. Conventional and emerging amblyopia treatment responses abide by the framework of BCM theory. Preclinical studies support that the dramatic reduction in cortical activity accompanying temporary retinal silencing can promote recovery from amblyopia even in adulthood, highlighting a promising therapeutic avenue.