Improving the treatment of amblyopia

Regions of the brain that support visual perception develop early in postnatal life when visual experience informs the proper arrangement of neural connections. Disruption of normal vision during this period, as can occur with cataracts, refractive errors or misaligned eyes, alters the spatial precision of neural connections. This derailment of normal development produces a vision disorder, amblyopia, that is the most common cause of blindness in children, and is the leading cause of monocular impairment in adults. Our research group published promising results for a novel strategy to treat severe amblyopia, which appears to work by reducing the level of visually-driven cortical activity. Our initial studies found that brief immersion into complete darkness produced recovery from amblyopia superior to that of conventional treatments. We later extended these findings to show that reversible pharmacological inactivation of the dominant eye promotes even faster recovery from amblyopia, and importantly at ages when conventional treatments fail to produce beneficial outcomes. Experiments in this proposal will address key parametric and mechanistic questions to facilitate translation of retinal inactivation as a treatment approach for amblyopia. We aim to delineate the time window during which recovery occurs, investigate possible neural mechanisms underlying recovery, and assess its safe application. We will also examine the efficacy of this treatment in a non-human primate model of amblyopia, a critical step for the possible translation of this therapy to humans. The remarkable recovery from amblyopia promoted by retinal inactivation holds promise for a completely new approach to treatment that could provide superior outcomes compared to available alternatives. Its success in humans would be transformative for pediatric ophthalmology. Such an advance holds enormous benefit to patients by improving visual health and broadening career and education opportunities.