Structural Basis of Amblyopia and Strabismus

弱视和斜视的结构基础

• 批准号: 6792747
• 负责人: JONATHAN C HORTON
• 金额: $ 52.59万
• 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 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6792747
• 关键词: Macaca mulatta; amblyopia; binocular vision; brain mapping; clinical research; cytochrome oxidase; enzyme activity; eye coordination disorder; human subject; perimetry; psychophysics; scotoma; sensory signal detection; space perception; structural biology; visual cortex; visual deprivation; visual fields; visual fixation

DESCRIPTION (provided by applicant): The ultimate objective of this project is to understand the neural mechanisms responsible for visual loss caused by two diseases: amblyopia and strabismus. Together, these conditions affect about 2% of the children in the United States. Amblyopia develops when one eye is deprived of normal visual stimulation during early childhood. For example, a congenital cataract impairs vision by preventing the retina from receiving clearly focused images. Even after the cataract is removed, the visual acuity in the eye remains poor, because visual deprivation has caused abnormal wiring of synaptic connections and disruption of cellular activity in the brain. In normal monkeys the synaptic connections in the primary visual cortex serving each eye are organized into a system of parallel, alternating bands, called ocular dominance columns. In some forms of amblyopia, these columns shrink and their cells lose responsiveness to the deprived eye. In Specific Aim #1, a metabolic label, cytochrome oxidase (CO), will be used to how ocular dominance columns are organized in humans, by examining post-mortem specimens of visual cortex obtained from patients with a history of visual loss in one eye. Patterns of metabolic activity will also be studied in amblyopia and strabismus, and in normal subjects in area V2, the next cortical area devoted to visual processing. In Specific Aim #2, connections will be traced from ocular dominance columns to area V2 in the macaque. The hypothesis is that a loss of projections from cells in the deprived eye's ocular dominance columns to area V2 is unimportant factor in amblyopia, because it prevents the normal transfer of visual information to higher centers. In Specific Aim #3, the neural mechanisms responsible for visual suppression will be examined. In strabismus, children fail to maintain normal alignment of the eyes. They avoid double vision by suppressing the image from one eye. How this occurs will be studied in strabismic macaques by testing their visual function and ocular fixation preference. Dichoptic perimetry will be employed to map patterns of visual suppression in the visual fields. After these psychophysical tests are completed, recordings will be made from single cells in awake animals, as they switch fixation back and forth between each eye. The goal will be to determine how the firing rate of cells is modulated by visual suppression. Iso-oriented and cross-oriented gratings will be used to search for binocular facilitation and suppression, and to test whether these effects depend upon which eye is perceptually dominant. Finally, areas of regional suppression in the visual fields will be correlated with patterns of CO activity in the ocular dominance columns. The hypothesis is that metabolic activity will be reduced in the suppressed eye's columns. New insights from these experiments into the structural basis of amblyopia and strabismus may lead to improved methods of preventing and treating these diseases.

描述（由申请人提供）：本项目的最终目标是了解由两种疾病引起的视力丧失的神经机制：弱视和斜视。这些情况加在一起影响了美国约2%的儿童。弱视是在儿童早期一只眼睛被剥夺了正常的视觉刺激时发生的。例如，先天性白内障通过阻止视网膜接收清晰聚焦的图像而损害视力。即使在白内障摘除后，眼睛的视力仍然很差，因为视觉剥夺会导致突触连接的异常布线和大脑细胞活动的中断。在正常的猴子中，初级视觉皮层中服务于每只眼睛的突触连接被组织成一个平行的、交替的带系统，称为眼优势柱。在某些形式的弱视中，这些柱萎缩，它们的细胞对剥夺的眼睛失去反应。在特定目标#1中，代谢标记细胞色素氧化酶（CO）将用于通过检查从单眼视力丧失史患者中获得的视皮层死后标本来研究人类眼优势柱的组织方式。代谢活动的模式也将在弱视和斜视，并在正常受试者的V2区，下一个皮层区域专门用于视觉处理。在具体目标#2中，将追踪猕猴中从眼优势列到V2区的连接。该假说认为，从剥夺眼的眼优势柱中的细胞到V2区的投射的损失是弱视的不重要因素，因为它阻止了视觉信息向更高中心的正常传递。在具体目标#3中，将检查负责视觉抑制的神经机制。在斜视中，儿童不能保持眼睛的正常对齐。它们通过抑制一只眼睛的图像来避免复视。这是如何发生的，将通过测试它们的视觉功能和眼睛固定偏好来研究。将采用分视视野检查来绘制视野中的视觉抑制模式。在这些心理物理测试完成后，将从清醒动物的单细胞中记录它们在每只眼睛之间来回切换注视的情况。我们的目标将是确定细胞的放电率是如何通过视觉抑制来调节的。等取向和交叉取向光栅将被用来搜索双眼促进和抑制，并测试这些影响是否取决于哪只眼睛是感知主导。最后，在视野中的区域抑制的区域将与CO活动的模式在眼优势柱。假设是代谢活动将在被抑制的眼柱中减少。从这些实验中对弱视和斜视的结构基础的新见解可能会导致预防和治疗这些疾病的改进方法。