Structural Basis of Amblyopia and Strabismus

描述(申请人提供)：双目视觉是一种自然的体验，我们认为它是理所当然的。来自每只眼睛的图像流在大脑中融合，创造出单一的世界视图。在出生的几周内，婴儿学会了将眼睛放在一起并移动，这样目标就可以准确地投射到每个视网膜上。一旦眼睛对准，双目深度知觉就开始出现。不幸的是，在2%的儿童中，眼球对准失败，导致斜视。当成年人的眼睛错位时，结果是复视或复视。当儿童出现斜视时，复视也会发生，但只是暂时的。几天之内，孩子们就会压制一张照片。这种感觉适应是有帮助的，因为它消除了复视。然而，它也是有害的，因为它剥夺了视觉系统维持眼睛对准所需的反馈。儿童可以忍受斜视，而不是通过调整眼部肌肉来重新调整眼球。由于长期的压抑，斜视患者通常会患上弱视，或称“懒眼”。这项研究项目的一个主要目标是了解大脑中如何发生压抑。最近，我们在人类患者身上进行了双眼视野图，以确定外斜视或眼睛向外偏斜时出现的视觉抑制模式。我们还饲养了患有外斜视的猴子，方法是在出生后削弱内直肌。这些动物表现出与人类几乎相同的视觉抑制模式。建立猕猴斜视模型是有价值的，因为它可以记录单个神经元的电放电，以确定抑制的基本神经机制。在特定的目标#1中，我们将记录患有斜视的猕猴的初级视觉皮质，其中抑制暗点已被绘制在其中，以比较单眼和双眼刺激时单个单位的反应。假说是，位于一只眼睛抑制暗点内的感受野细胞可能对单眼刺激有反应，但当另一只优势眼也受到刺激时，细胞将被抑制。在特定的目标#2中，我们将研究患有斜视的人类受试者如何决定用哪只眼睛来观察他们视觉环境中的目标。在绘制抑制暗点图后，受试者将看到只有右眼、左眼或可能的任一只眼可见的外围目标。对于视野中的每个位置，我们将确定获得目标的眼睛是否是感知目标的眼睛。这项实验将揭示斜视患者是否有时用一只眼睛来获取目标位置，另一只眼睛则用来扫视它。在具体目标#3中，我们将研究控制眼球运动的脑干中枢上丘细胞的结构和特性，以探索控制斜视灵长类动物眼跳的神经机制。从这项工作中获得的知识可能为制定预防和治疗斜视的策略提供新的基础。

DESCRIPTION (provided by applicant): Binocular vision is such a natural experience that we take it for granted. The stream of images from each eye is fused within the brain to create a single view of the world. Within weeks of birth, infants learn to align and move their eyes together, so that targets are projected accurately onto each retina. Once the eyes become aligned, binocular depth perception begins to emerge. Unfortunately, in 2% of children, ocular alignment fails, giving rise to strabismus. When the eyes become misaligned in adults, the result is double vision or diplopia. When strabismus develops in children, diplopia also occurs, but only transiently. Within days, children suppress one image. This sensory adaptation is helpful, because it eliminates diplopia. However, it is also harmful, because it deprives the visual system of the feedback required to maintain ocular alignment. Instead of adjusting the eye muscles to re-align the globes, children tolerate strabismus. The deviated eye often develops amblyopia, or "lazy" eye, because of chronic suppression. A major goal of this research project is to learn how suppression occurs in the brain. Recently, we have performed dichoptic visual field mapping in human patients to define the pattern of visual suppression that occurs in exotropia, or outwards eye deviation. We have also raised monkeys with exotropia, by weakening the medial rectus eye muscles after birth. These animals display patterns of visual suppression nearly identical to those in humans. To have a macaque model of strabismus is valuable, because it is possible to record the electrical discharges of single neurons to define the basic neural mechanism of suppression. In Specific Aim #1, we will record from the primary visual cortex of macaques with strabismus, in whom suppression scotomas have been previously mapped, to compare the responses of single units during monocular versus binocular stimulation. The hypothesis is that cells with receptive fields located within an eye's suppression scotoma may respond to monocular stimulation, but will be inhibited when the other, dominant eye is also stimulated. In Specific Aim #2, we will examine how human subjects with strabismus decide which eye to use to look at targets in their visual environment. After mapping of suppression scotomas, subjects will be presented with peripheral targets visible to only the right eye, the left eye, or potentialy either eye. For each location in the visual field, we will determine if the eye that acquired the target was the eye that perceived the target. This experiment will reveal whether people with strabismus sometimes use one eye to acquire target location, and the other eye to saccade to it. In Specific Aim #3, we will investigate the topography and properties of cells in the superior colliculus, a brainstem center that controls eye movements, to probe the neural mechanisms governing eye selection for saccades in primates with strabismus. Knowledge gained from this work may provide a new basis for developing strategies to prevent and treat strabismus.