BINOCULAR FUNCTION IN STRABISMUS

项目摘要 “直视我的眼睛”，一位家长告诫说，但对一些孩子来说，这是不可能的，因为一只眼睛是 偏离了在这种情况下，被称为斜视，立体视觉可能会丢失，斜视眼可能会发展 弱视长期后果包括眼手协调能力下降，生活质量下降， 就业歧视、社会偏见和心理困扰。本项目的总体目标是 去发现为什么有些孩子的双眼视觉会不正常当儿童失去融合时，他们会避免复视 通过抑制每只眼睛看到的部分视野。这些地区的发展， 抑制暗点，阻止了通常会引起眼外眼调节的误差信号 让眼睛恢复正常眼科医生进行手术，以调整眼睛，但成功 率远远不能令人满意，主要是因为持续的压制剥夺了儿童的动力， 恢复聚变。为了找到更好的治疗方法，必须了解抑制的神经基础。这 项目采用了一种平移的方法：斜视患者进行研究，以表征他们的缺陷， 然后在患有实验性斜视的非人类灵长类动物中探索这些缺陷， 与真实的疾病非常相似。在目标#1中，研究集中于外斜视儿童，即向外斜视， 一只眼睛的偏差。它通常是间歇性的，但眼科医生倾向于建议手术，因为担心 间歇性外斜视可发展为持续性外斜视，导致双眼功能的永久性丧失。 在一项纵向观察性队列研究中，患者将配备可穿戴眼动仪， 日常活动过程中外斜视发作的频率。使用该设备的可行性 追踪个体患者的疾病严重程度。将在5年内收集数据， 阐明这种情况的自然历史。在目标2中，一种新的化学遗传学技术将用于沉默 投射到上级丘的视网膜神经节细胞。这些细胞在生成眼睛中的作用 移动是未知的，因为到目前为止，还没有任何方法可以选择性地和可逆地阻止它们。 将对外向性猴子进行检查，以确定对感受野特性和能力的影响 交替扫视在目标#3中，抑制暗点将在猴子中进行二分映射， 外斜视一旦他们的布局建立，记录将在初级视觉皮层，比较 单细胞对单眼与双眼刺激的反应。对于双眼测试，刺激将被传递到 到一只眼睛的感受野和另一只眼睛的位置，该位置被 眼偏斜这一假说认为，细胞的感受野位于感知区域， 在双眼观察条件下被抑制的人在双眼刺激期间的反应比在双眼观察条件下被抑制的人更弱。 在单眼刺激期间。这些皮层记录，第一次在警觉的，行为正常的猴子中进行， 斜视，可以揭示抑制的神经基础相关的单细胞放电与视觉感知。

Project Summary “Look me straight in the eye” a parent exhorts, but for some children it is impossible because one eye is deviated. In this condition, known as strabismus, stereovision may be lost and the deviated eye may develop amblyopia. Long term consequences include reduced eye-hand coordination, diminished quality of life, employment discrimination, social prejudice, and psychological distress. The overarching goal of this project is to discover why normal binocular vision fails in some children. When children lose fusion, they avoid diplopia by suppressing portions of the visual field seen with each eye. The development of these regions, called suppression scotomas, blocks the error signal that would normally induce an adjustment in extraocular eye muscle tone to bring the eyes back together. Ophthalmologists perform surgery to align eyes, but success rates are far from satisfactory, largely because the persistence of suppression robs children of the drive to recover fusion. To find better treatments, it is imperative to understand the neural basis of suppression. This project uses a translational approach: patients with strabismus are studied to characterize their deficits, and then these deficits are probed in nonhuman primates raised with an experimental form of strabismus that closely resembles the real disease. In Aim #1, studies are focused on children with exotropia, an outwards deviation of one eye. It is usually intermittent, but ophthalmologists tend to recommend surgery, for fear that an intermittent exotropia may progress to become constant, resulting in permanent loss of binocular function. In a longitudinal observational cohort study, patients will be outfitted with a wearable eyetracker to document the frequency of episodes of exotropia during the course of daily activities. The feasibility of using this device to track disease severity in individual patients will be investigated. Data will be collected over 5 years to elucidate the natural history of this condition. In Aim #2, a new chemogenetic technique will be used to silence retinal ganglion cells that project to the superior colliculus. The role these cells play in generating eye movements is unknown, because until now, no method has existed to selectively and reversibly block them. Exotropic monkeys will be examined to determine the impact on receptive field properties and the ability to make alternating saccades. In Aim #3, suppression scotomas will be mapped dichoptically in monkeys with exotropia. Once their layout is established, recordings will be made in the primary visual cortex, to compare responses of single cells to monocular vs. binocular stimulation. For binocular testing, stimuli will be delivered to the receptive field in one eye and to a location in the other eye that is displaced by the magnitude of the ocular deviation. The hypothesis is that cells with their receptive field located in regions where perception is suppressed under binocular viewing conditions will respond more weakly during binocular stimulation than during monocular stimulation. These cortical recordings, the first conducted in alert, behaving monkeys with strabismus, may reveal the neural basis of suppression by correlating single cell firing with visual perception.