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

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Figure 1:. Monocular deprivation results in LTD of thalamocortical synapses.

(Left) In normally reared animals, cortical neurons (green) receive inputs from both eyes (blue and yellow). (Right) If one eye is monocularly deprived, this typically well correlated input is replaced with uncorrelated noise and results in LTD of inputs onto cortical neurons. This will result in reduced cortical responsiveness to stimulation of this eye even after the period of deprivation.

Figure 2:. Interpreting the pathogenesis of amblyopia and responses to visual deprivation through the lens of BCM theory

(A) The BCM theory postulates that synaptic strength is modified such that postsynaptic activity below a threshold (*) will result in weakening of synaptic strength (LTD), while activity above this threshold results in long-term potentiation (LTP). The activity threshold itself can be modified based on previous neuronal activity. Monocular deprivation reduces activity in the visual pathway serving that eye, leading to LTD of inputs. (B) Various forms of visual deprivation (including occlusion or blurring of the fellow eye, anti-suppression therapy, complete darkness, fellow eye injury or loss, and retinal inactivation) may decrease cortical activity and subsequently shift the modification threshold to allow for potentiation of inputs serving the amblyopic eye.