Repetitive visual stimulation enhances recovery from severe amblyopia

Abstract

Severe amblyopia, characterized by a significant reduction in visual acuity through the affected eye, is highly resistant to reversal in adulthood. We have previously shown that synaptic plasticity can be reactivated in the adult rat visual cortex by dark exposure, and the reactivated plasticity can be harnessed to promote the recovery from severe amblyopia. Here we show that deprived-eye visually evoked responses are rapidly strengthened in dark-exposed amblyopes by passive viewing of repetitive visual stimuli. Surprisingly, passive visual stimulation rapidly enhanced visually evoked responses to novel stimuli and enhanced the recovery from severe amblyopia driven by performance of active visual discriminations. Thus a series of simple, noninvasive manipulations of visual experience can be used in combination to significantly guide the recovery of visual response strength, selectivity, and spatial acuity in adult amblyopes.

Rapid recovery from the effects of early monocular deprivation is enabled by temporary inactivation of the retinas

“…Dark exposure (to lower the plasticity threshold) followed by repetitive (55) or dichoptic (56) visual training exercises (to use binocular cooperativity to strengthen weak synapses in V1) offers a neurobiologically sound alternative to reverse occlusion (patching) as a treatment for amblyopia. However, previous studies in kittens have found that very brief daily light exposure eliminated the therapeutic effects of an otherwise uninterrupted 10-d period of darkness (32).…”

Optimization of visual training for full recovery from severe amblyopia in adults

“…Interestingly, visual perceptual learning has been reported to potentiate the strength of intracortical synapses, and raise the ceiling for further potentiation of thalamo-cortical synapses in primary visual cortex of binocular rodents (Hager and Dringenberg 2010;Sale et al 2011;Hager et al 2015). Similar stimulus selectivity is observed in the enhancement of VEP amplitudes and single neuron responses following passive visual stimulation in rodents and humans (Frenkel et al 2006;Cooke and Bear 2010;Clapp et al 2012;Montey et al 2013;Kaneko and Stryker 2014).…”

“…Long-term monocular deprivation initiated early in postnatal life has been shown to weaken the strength and selectivity of visually evoked responses in primary visual cortex and reduce visual acuity in many species (Wiesel and Hubel 1963;Kim and Bonhoeffer 1994;Liao et al 2004;Montey et al 2013). The anatomical and functional deficits induced by early chronic monocular deprivation are particularly difficult to reverse (Liao et al 2004;Pizzorusso et al 2006;Iny et al 2006;He et al 2007).…”

“…Long-Evans rats received monocular lid suture (under 50 mg/ 10 mg/kg, i.p ketamine/xylazine) from post-natal day 14 (early onset) or post-natal day 28 (late onset) until adulthood ( post-natal day 185) to induce severe amblyopia (He et al 2007;Montey et al 2013). A two alternative, forced choice, waterbased spatial frequency detection task (modified from Prusky et al 2000) was used to first assess visual detection thresholds of the nondeprived eye.…”

“…In addition, dark exposure scales up excitatory synapses on principle neurons, increases visual cortex excitability, and expands the integration window for spike-timing dependent plasticity (Goel and Lee 2007;He et al 2007;Guo et al 2012). The success of dark rearing, and other manipulations, such as environmental enrichment, to promote the recovery from amblyopia in rodents and felines (He et al 2006;Sale et al 2007;Maya Vetencourt et al, 2008;Duffy and Mitchell 2013;Stodieck et al, 2014) likely depends on the reactivation of these and other forms of activity-dependent plasticity (Kuo and Dringenberg 2009;Harauzov et al 2010;Mainardi et al 2010;Djurisic et al 2013) that are engaged by visual perceptual learning (Baroncelli et al 2012;Montey et al 2013).…”