Structural Basis of Amblyopia and Strabismus

项目描述（由申请人提供）：该项目的最终目的是了解弱视和斜视两种疾病导致视力丧失的神经机制。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正常的视觉刺激时形成的。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。即使在摘除白内障后，眼睛的视力仍然很差，因为视觉剥夺导致突触连接的异常连接和大脑细胞活动的中断。在正常猴子的初级视觉皮层中，服务于每只眼睛的突触连接被组织成一个平行、交替的带状系统，称为眼优势柱。在某些形式的弱视中，这些柱子收缩，它们的细胞对被剥夺的眼睛失去反应。在Specific Aim #1中，代谢标签细胞色素氧化酶（CO）将通过检查从单眼视力丧失病史的患者获得的死后视觉皮层标本，用于研究人类的眼优势柱是如何组织的。弱视和斜视的代谢活动模式也将被研究，在正常受试者的V2区，下一个专门用于视觉处理的皮质区域。在具体目标#2中，将追踪猕猴从眼优势柱到V2区域的连接。该假说认为，被剥夺的眼睛的眼优势柱上的细胞向V2区投射的丧失是弱视的一个不重要因素，因为它阻碍了视觉信息向更高中心的正常传递。在Specific Aim #3中，我们将研究视觉抑制的神经机制。在斜视中，儿童不能保持眼睛的正常排列。他们通过抑制一只眼睛的图像来避免复视。我们将通过测试斜视猕猴的视觉功能和注视偏好来研究这种现象是如何发生的。双视视距法将用于绘制视野中视觉抑制的模式。在这些心理物理测试完成后，将对清醒动物的单个细胞进行记录，因为它们在每只眼睛之间来回切换注视。目标将是确定细胞的放电速率是如何通过视觉抑制来调节的。等向和交叉取向光栅将用于寻找双眼促进和抑制，并测试这些影响是否取决于哪只眼睛在感知上占主导地位。最后，区域抑制的领域在视野将与模式相关的CO活性在眼优势柱。假设是，在受到抑制的眼柱中，代谢活动会减少。这些实验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方法的改进。

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.