Correction of amblyopia in cats and mice after the critical period

Abstract

Monocular deprivation early in development causes amblyopia, a severe visual impairment. Prognosis is poor if therapy is initiated after an early critical period. However, clinical observations have shown that recovery from amblyopia can occur later in life when the non-deprived (fellow) eye is removed. The traditional interpretation of this finding is that vision is improved by relieving interocular suppression in primary visual cortex. However, an alternative explanation is that elimination of activity in the fellow eye establishes conditions in visual cortex that enable the weak connections from the amblyopic eye to gain strength. Here we show in cats and mice that temporary inactivation of the fellow eye is sufficient to promote a full and enduring recovery from amblyopia at ages when conventional treatments fail. Thus, connections serving the amblyopic eye are capable of substantial plasticity beyond the critical period, and this potential is unleashed by reversibly silencing the fellow eye.

The Impact of Brief Monocular Retinal Inactivation on the Central Visual System During Postnatal Development

“…Just as an inactive muscle fiber rapidly recovers size when the temporarily silenced motoneuron activity is restored, we wondered if dLGN cell size changes ascribed to reduced retinal activity is similarly transient. In previous studies, we demonstrated that felloweye retinal inactivation applied at 10 weeks of age can promote recovery from the effects of a prior long-term MD, and critically the inactivation produced no lasting detriment to the inactivated eye or to the dLGN layers connected to it (Duffy et al, 2018; Fong et al, 2021; DiCostanzo et al, 2020). We were therefore interested to test the durability of the effect of retinal inactivation by providing a subset of animals with binocular vision after they received 10 days of retinal inactivation applied at 10 weeks of age.…”

“…It is worth pointing out that the restoration of normal dLGN soma size and the recovery of VEPs after inactivation occurred at an age (i.e. 10 weeks old) when inactivation of the fellow eye can promote full recovery from the anatomical and physiological effects of long-term MD (Duffy et al, 2018; Fong et al, 2021). The current findings indicate that the modifications elicited by inactivation do not to have a lasting negative impact on the visual system, and instead appear to elicit a constellation of modifications that avail an opportunity for recovery from the neural modifications provoked by amblyogenic rearing.…”

“…Following a long-term MD in which ocular dominance is shifted strongly in favor of the non-deprived eye, inactivation of the stronger eye in both mice and cats can promote recovery of visually-driven cortical responses elicited by the weaker eye (Fong et al, 2021). Similar recovery occurs in the cat dLGN, where deprived neurons rendered smaller by MD recover to their normal size when the non-deprived eye is inactivated for 10 days (Duffy et al, 2018).…”

“…Recent mouse and cat studies have demonstrated that post-critical period recovery from MD can occur if the dominant eye’s retina is temporarily inactivated with intravitreal microinjection of tetrodotoxin (TTX), a voltage-gated sodium channel blocker that can reversibly eliminate retinal ganglion cell activity (Duffy et al, 2018; Fong et al, 2021). Following a period of MD, inactivation of the dominant (fellow) eye restores neural responses to the weaker one, and promotes recovery from the MD-induced atrophy of neuron soma size in the dLGN.…”

Visual experience has opposing influences on the quality of stimulus representation in adult primary visual cortex

“…Depression of deprived inputs occurs at a synaptic level and outlasts the perturbation. On the other hand, the same peripheral perturbation in adults does not induce a rapid decrease in response strength, although potentiation of the intact input does proceed 4,5 . Furthermore, in the young, the impact of deprivation on excitatory neuron activity levels is compensated for by a decrease in evoked inhibitory neuron activity.…”