Optimized visual recovery in adult human amblyopia through binocular deprivation

 描述(申请人提供)：出生后早期眼睛视觉输入的不对称会导致弱视，这是人类单眼失明的最常见基础。在弱视中，非弱视眼控制着双眼视觉皮质的神经元反应，而弱视眼刺激皮质神经元的能力可能会减弱到功能性失明的程度。以前尝试恢复成人弱视的视力取得了一定的成功，我们认为这在很大程度上是由于皮质发育过程中突触可塑性的显著降低。我们认为，成人弱视的最佳恢复需要两个阶段：1)重新激活成人弱视皮质中的突触可塑性(允许步骤)；2)集中视觉体验以刺激知觉学习(指导步骤)。包括昆兰实验室在内的两个实验室(伊莉莎白·昆兰是这项拟议工作的顾问)最近表明，成年后双眼视觉剥夺(BD)增强了实验动物成年大脑皮质中突触的可塑性。此外，在深度弱视动物模型中，BD先于重复视觉体验刺激空间敏锐度的恢复。在这里，我们建议将这一发现转化为治疗人类弱视的方法。我们建议使用5天和10天的双眼视觉剥夺(即生活在完全黑暗中)来促进弱视视觉皮质的突触可塑性，然后进行8周的视觉知觉学习，以刺激视觉功能的恢复。虽然视觉知觉学习之前已经被证明可以增强弱视成年人的视觉功能，但这种进步是缓慢和适度的。我们预测，双眼视觉剥夺的弱视视觉系统的“预治疗”将提高弱视学习诱导恢复的幅度和/或时间进程。为检验这一假设而组建的研究团队是对视觉功能进行全面分析的理想组合，包括心理物理学和生理学，以跟踪实验期间关键里程碑的视觉功能变化。如果成功，这项工作将改变成人弱视的治疗方法，并将注意力集中在增强突触可塑性作为中枢神经系统治疗和训练的辅助手段的重要性上。从这项工作中获得的见解可以扩展到斜视、眼动控制障碍以及创伤性脑损伤后最佳神经功能的恢复。拟议中的实验还将率先在人类弱视中使用双眼视觉剥夺，并制定实施标准，包括参与者护理、监测和隔离期间的安全性。

 DESCRIPTION (provided by applicant): An asymmetry in the visual input across the eyes early in postnatal life causes amblyopia, the most common basis of uniocular blindness in humans. In amblyopia, the nonamblyopic eye dominates control of neuronal responses in the binocular visual cortex, while the ability of the amblyopic eye to stimulate cortical neurons may weaken to the point of functional blindness. Previous attempts to recover vision in adult amblyopes have had modest success, and we propose this is due in large part to the significant reduction of synaptic plasticity that occurs during cortical development. We propose that optimizing recovery from amblyopia in adulthood requires a two stage process: 1) the reactivation of synaptic plasticity in the adult amblyopic cortex (permissive step) and 2) focused visual experience to stimulate perceptual learning (instructive step). Two labs, including the Quinlan lab (Elizabeth Quinlan is a consultant in the proposed work) have recently shown that binocular visual deprivation (BD) in adulthood enhances synaptic plasticity in the adult cortex of experimental animals. In addition, BD prior to repetitive visual experience stimulates the recovery of spatial acuity in animal models of deep amblyopia. Here we propose to translate this finding to the treatment of amblyopia in humans. We propose to use 5 and 10 days of binocular visual deprivation (in other words, living in complete darkness) to promote synaptic plasticity in the amblyopic visual cortex, followed by 8 weeks of visual perceptual learning, to stimulate the recovery of visual function. While visual perceptual learning has been previously shown to enhance visual function in amblyopic adults, the gains are slow and modest. We predict that "pre-treatment" of the amblyopic visual system with binocular visual deprivation will enhance the magnitude and/or time course of learning-induced recovery from amblyopia. The team of investigators assembled to test this hypothesis is ideally composed for a comprehensive analysis of visual functions, including both psychophysics and physiology, to track changes in visual function at key milestones during the experiment. If successful, this work would transform therapy for adult amblyopia, and focus attention on the importance of enhancing synaptic plasticity as an adjunct to treatment and training in the central nervous system. Insights gained from this work could be extended to strabismus, eye movement control disorders, and the restoration of optimal neural function after damage from traumatic brain injury. The proposed experiments will also pioneer the use of binocular visual deprivation in human amblyopes, and develop standards for implementation, including participant care, monitoring, and safety during sequestration.