期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：49
页码：14139-14144
DOI：10.1073/pnas.1613279113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceNormal development of the visual cortex depends critically on early life visual experience. In humans, a disparity in the quality of vision between two eyes during infancy or early childhood leads to a visual impairment called amblyopia. In animal models, amblyopia can be induced early in life using a brief period of monocular deprivation via eyelid closure. Here we show in two evolutionarily divergent species that experimental amblyopia can be rapidly corrected if binocular visual experience is restored after temporarily silencing the retinas with a local anesthetic. These findings point the way to an approach for clinical management of amblyopia with advantages over the current standard of care. A half-century of research on the consequences of monocular deprivation (MD) in animals has revealed a great deal about the pathophysiology of amblyopia. MD initiates synaptic changes in the visual cortex that reduce acuity and binocular vision by causing neurons to lose responsiveness to the deprived eye. However, much less is known about how deprivation-induced synaptic modifications can be reversed to restore normal visual function. One theoretically motivated hypothesis is that a period of inactivity can reduce the threshold for synaptic potentiation such that subsequent visual experience promotes synaptic strengthening and increased responsiveness in the visual cortex. Here we have reduced this idea to practice in two species. In young mice, we show that the otherwise stable loss of cortical responsiveness caused by MD is reversed when binocular visual experience follows temporary anesthetic inactivation of the retinas. In 3-mo-old kittens, we show that a severe impairment of visual acuity is also fully reversed by binocular experience following treatment and, further, that prolonged retinal inactivation alone can erase anatomical consequences of MD. We conclude that temporary retinal inactivation represents a highly efficacious means to promote recovery of function.
