Optimized visual recovery in adult human amblyopia through binocular deprivation

 描述（由申请人提供）：出生后早期眼睛视觉输入的不对称性导致弱视，这是人类单眼失明的最常见基础。在弱视中，非弱视眼支配双眼视觉皮层中的神经元反应的控制，而弱视眼刺激皮层神经元的能力可能减弱到功能性失明的程度。以前的尝试，以恢复视力的成人弱视有适度的成功，我们认为这在很大程度上是由于在皮层发育过程中发生的突触可塑性的显着减少。我们提出，在成年期优化弱视的恢复需要两个阶段的过程：1）成人弱视皮层中突触可塑性的重新激活（许可步骤）和2）集中的视觉体验刺激知觉学习（指导步骤）。包括昆兰实验室（伊丽莎白·昆兰是拟议工作的顾问）在内的两个实验室最近表明，成年期双眼视觉剥夺（BD）增强了实验动物成年皮质的突触可塑性。此外，BD之前，重复的视觉经验刺激恢复的空间敏锐度在深度弱视的动物模型。在这里，我们建议将这一发现转化为人类弱视的治疗。我们建议用5天和10天的双眼视觉剥夺（换句话说，生活在完全黑暗中）来促进弱视视皮层的突触可塑性，然后进行8周的视知觉学习，以刺激视觉功能的恢复。虽然视觉感知学习先前已被证明可以增强弱视成年人的视觉功能，但这种增益是缓慢和适度的。我们预测，“预处理”的弱视视觉系统与双眼视觉剥夺将提高幅度和/或时间过程中学习诱导的弱视恢复。为测试这一假设而组建的研究人员团队是对视觉功能进行全面分析的理想组成，包括心理物理学和生理学，以跟踪实验过程中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，眼球运动控制障碍，以及创伤性脑损伤后最佳神经功能的恢复。拟议的实验还将率先在人类弱视患者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。

 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.