Structural Basis of Amblyopia and Strabismus

弱视和斜视的结构基础

• 批准号: 7650334
• 负责人: JONATHAN C HORTON
• 金额: $ 38.63万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7650334
• 关键词: Affect; Amblyopia; Back; Behavior; Binocular Vision; Brain; Cells; Characteristics; Child; Color; Cranial Nerves; Data; Defect; Depth Perception; Development; Diplopia; Disease; Enzymes; Esotropia; Event; Exhibits; Exotropia; Eye; Eye diseases; Failure; Goals; Grant; Human; Image; Laboratories; Lead; Learning; Life; Location; Macaca; Maps; Mediating; Metabolic; Metabolism; Methods; Microelectrodes; Mitochondria; Muscle Tonus; Newborn Infant; Ocular dominance columns; Patients; Pattern; Play; Population; Primates; Research Project Grants; Rest; Retina; Role; Scotoma; Signal Transduction; Staining method; Stains; Strabismus; Stream; Testing; Vision; Visual; Visual Cortex; Visual Fields; Visual Pathways; Visual system structure; area striata; awake; base; cohort; cost; cytochrome c oxidase; experience; fovea centralis; human subject; infancy; monocular; neuromechanism; nonhuman primate; oculomotor; prevent; public health relevance; relating to nervous system; research study; response; retinotopic; stereoscopic; visual map; visual motor; visual stimulus

Description (provided by applicant): 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. PUBLIC HEALTH RELEVANCE This project will determine how children with strabismus avoid double vision by suppressing signals emanating from local regions of the retina in each eye. Elucidating the mechanism of visual suppression may lead to better methods to prevent and treat strabismus.

描述（由申请人提供）：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。其特征是眼睛错位。关键是眼位不正的发生通常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的失败。该项目的目标是阐明导致斜视的大脑功能缺陷。斜视儿童通过使用视觉抑制来避免看到两个图像，以立体视觉为代价。如果抑制在一只眼睛中保持恒定，而不是在眼睛之间交替，他们也可能发展为弱视。视觉抑制是斜视发展的关键因素，因为它消除了通过融合单独图像进行补偿的驱动力。目前还不清楚视觉抑制是如何发生的，甚至是来自斜视眼的信号在视觉通路中的何处被阻断。本基金的第一个具体目标是绘制大量具有常见斜视形式的人类受试者的视野图：婴儿型内斜视、反射性内斜视和外斜视。该测试将在分视条件下进行，通过向佩戴彩色滤光片的受试者的每只眼睛呈现不同颜色的图像。这些实验将揭示视野的哪些部分被每只眼睛感知。第二个具体的目标是映射在斜视的猕猴提出的双视视野。猕猴在视觉系统的组织和功能上与人类极为相似。这一目标将确定是否有斜视的猕猴表现出类似于人类的抑制暗点。在非人类灵长类动物中进行实验的优势在于，可以在视觉皮层中进行微电极研究，以探索视觉抑制的神经基础。第三个具体目标是进行电生理记录清醒，斜视猕猴，而他们正在寻找与双眼的视觉刺激，了解如何在单细胞水平的双目相互作用引起抑制暗点。将在两个半球的初级视觉皮层（V1）的不同区域进行记录，以将单细胞记录与先前映射的抑制暗点相关联。第四个具体目标是检查斜视猕猴V1的代谢活动模式。服务于每只眼睛的输入被组织成称为眼优势列的交替带。斜视诱导异常染色模式的线粒体酶，细胞色素氧化酶（CO），在眼优势柱。将记录每个V1期间的CO活性模式，并与行为映射视野中的抑制模式进行比较。如果存在匹配，则将确定抑制是由抑制暗点内服务于非感知眼的细胞列中的活性降低介导的。该项目将确定斜视儿童如何通过抑制每只眼睛视网膜局部区域发出的信号来避免复视。阐明视觉抑制的机制可能会导致更好的方法来预防和治疗斜视。