Structural Basis of Amblyopia and Strabismus

斜视是一种在1-2%的儿童中发展的疾病，影响许多人的余生。是 以眼睛的错位为特征。关键的一点是，眼位不正通常发生在 没有任何颅神经异常或眼睛的内在疾病。主要的罪魁祸首是 负责维持双眼融合的神经机制这个项目的目标是阐明 导致斜视的大脑功能缺陷。患有斜视的儿童避免看到两个图像， 使用视觉抑制，以立体视觉为代价。如果抑制在一只眼睛中保持恒定， 比眼睛之间的交替，他们也可能发展为弱视。视觉抑制是 斜视的发展，因为它消除了通过融合单独图像来补偿的驱动力。是 不知道视觉抑制是如何发生的，甚至不知道来自斜视眼的信号在视觉中被阻挡在哪里。 通路这项资助的第一个具体目标是绘制大量人类受试者的视野图 具有常见形式的斜视：婴儿型内斜视、斜视性内斜视和外斜视。测试 将在双视条件下完成，通过向佩戴的受试者的每只眼睛呈现不同颜色的图像， 彩色滤光片这些实验将揭示视野的哪些部分被每只眼睛感知。的 第二个具体目的是绘制患有斜视的猕猴的双眼视物分离视野。猕猴是 在视觉系统的组织和功能上与人类极为相似。这一目标将决定， 患有斜视的猕猴表现出与人类相似的抑制暗点。的优点 在非人类灵长类动物中进行实验的一个重要原因是，人们可以在视觉皮层中进行微电极研究 探索视觉抑制的神经基础第三个具体目标是进行电生理检查， 记录在清醒的，斜视猕猴，而他们正在寻找与视觉刺激的双眼，以了解如何 单细胞水平上的双眼相互作用引起抑制暗点。录音将在 在两个半球的初级视觉皮层（V1）的不同区域，将单细胞记录与 先前映射的抑制暗点。第四个具体目标是检查代谢模式， 斜视猕猴的V1活动。服务于每只眼睛的输入被组织成交替的频带 称为眼优势柱。斜视引起线粒体异常染色模式 酶，细胞色素氧化酶（CO），在眼优势列。CO活性的模式在每个 将记录V1并与行为映射视野中的抑制模式进行比较。 如果有匹配，它将确定抑制是由细胞列中活性的降低介导的 在抑制暗点内服务于无感知的眼睛。

Strabismus is a disease that develops in 1-2% of children, affecting many for the rest of their lives. It is characterized by misalignment of the eyes. The crucial point is that the ocular misalignment usually occurs without any abnormality of the cranial nerves or intrinsic disorder of the eyes. The primary culprit is a failure of the neural mechanisms responsible for maintaining binocular fusion. The goal of this project is to elucidate the defects in brain function responsible for strabismus. Children with strabismus avoid seeing two images by using visual suppression, at the cost of stereovision. If the suppression remains constant in one eye, rather than alternating between the eyes, they may also develop amblyopia. Visual suppression is a critical factor in the development of strabismus, because it eliminates the drive to compensate by fusing separate images. It is unknown how visual suppression occurs, or even where signals from the deviated eye are blocked in the visual pathway. The first specific aim in this grant is to map the visual fields in a large population of human subjects with common forms of strabismus: infantile esotropia, accommodative esotropia, and exotropia. The testing will be done under dichoptic conditions, by presenting different colored images to each eye of subjects wearing colored filters. These experiments will reveal which portions of the visual field are perceived by each eye. The second specific aim is to map dichoptic visual fields in macaques raised with strabismus. The macaque is extremely similar to the human in the organization and function of its visual system. This aim will determine if macaques with strabismus exhibit suppression scotomas similar to those in humans. The advantage of pursuing experiments in nonhuman primates is that one can perform microelectrode studies in the visual cortex to probe the neural basis of visual suppression. The third specific aim is to undertake electrophysiological recordings in awake, strabismic macaques while they are looking with both eyes at visual stimuli, to learn how binocular interactions at the level of single cells give rise to suppression scotomas. Recordings will be made in different regions of the primary visual cortex (V1) in both hemispheres, to correlate single cell recordings with previously mapped suppression scotomas. The fourth specific aim is to examine the pattern of metabolic activity in V1 of macaques with strabismus. Inputs serving each eye are organized into alternating bands called ocular dominance columns. Strabismus induces abnormal staining patterns of the mitochondrial enzyme, cytochrome oxidase (CO), in ocular dominance columns. The pattern of CO activity throughout each V1 will be documented and compared with the pattern of suppression in the visual field mapped behaviorally. If there is a match, it will establish that suppression is mediated by a reduction of activity in columns of cells serving the non-perceiving eye within a suppression scotoma.