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）：Strabismus是一种在1-2％的儿童中发展的疾病，影响了许多人的余生。它的特征是眼睛不对。关键点是，眼睛未对准通常不会出现颅神经或眼睛内在障碍的任何异常。罪魁祸首是负责维持双眼融合的神经机制的失败。该项目的目的是阐明负责斜视的大脑功能缺陷。具有斜视的儿童避免使用视觉抑制，以立体表演为代价。如果在一只眼中抑制保持恒定，而不是在眼睛之间交替，则它们也可能发展出弱视。视觉抑制是斜视发展的关键因素，因为它通过融合单独的图像来消除驱动力。尚不清楚视觉抑制是如何发生的，甚至在视觉途径中封闭了偏离眼睛的信号。这笔赠款的第一个具体目的是绘制大量人类受试者的视野，具有常见的斜视形式：婴儿性叶绿节，可容纳性肝癌和外型。测试将在二分条件下进行，通过向佩戴彩色过滤器的受试者的每只眼睛展示不同的彩色图像。这些实验将揭示每只眼睛感知视野的哪些部分。第二个具体目的是绘制用斜视提出的猕猴中的二氯视野。猕猴与其视觉系统的组织和功能中的人类非常相似。这个目标将确定猕猴是否表现出与人类类似的抑制scotomas。在非人类灵长类动物中追求实验的优点是，可以在视觉皮层中进行微电极研究以探测视觉抑制的神经基础。第三个具体目的是在醒着，斜视的猕猴中进行电生理记录，同时双眼看着视觉刺激，以了解如何在单个细胞水平上的双筒望远镜相互作用产生抑制scotomas。记录将在两个半球的主要视觉皮层（V1）的不同区域进行，以将单细胞记录与先前映射的抑制Scotomas相关。第四个具体目的是检查具有斜视的猕猴V1中的代谢活性模式。使用每只眼睛的输入被组织成称为Ocular Primation Contrs的交替带。斜视在眼部优势柱中诱导线粒体酶，细胞色素氧化酶（CO）的异常染色模式。将记录每个V1中的CO活动模式，并将其与视野在行为上映射的抑制模式进行比较。如果有匹配，它将确定抑制是通过在抑制Scotoma中提供非可感知眼睛的细胞列的活性的减少来介导的。公共卫生相关性该项目将通过抑制每只眼睛的视网膜当地地区发出的信号来避免双重视力的儿童如何避免双重视力。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。