Structural Basis of Amblyopia and Strabismus

弱视和斜视的结构基础

基本信息

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
项目类别：
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

项目摘要

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）：该项目的最终目标是了解导致两种疾病引起的视觉丧失的神经机制：弱视和斜视。这些条件共同影响了美国约2％的儿童。当一只眼睛在儿童早期被剥夺正常视觉刺激时，弱视就会发展。例如，先天性白内障通过防止视网膜收到明确集中的图像来损害视力。即使去除白内障，眼睛的视力仍然很差，因为视觉剥夺导致突触连接的异常接线和大脑中细胞活性的破坏。在正常的猴子中，将每只眼睛的一级视觉皮层中的突触连接组织成一个平行的交替带系统，称为眼部优势柱。在某些形式的弱视中，这些列会收缩及其细胞对被剥夺的眼睛失去反应。在特定的目标＃1中，代谢标签细胞色素氧化酶（CO）将通过检查从一只眼睛视觉损失病史的患者获得的视觉皮层的验尸标本，用于在人类中如何在人类中组织。还将在弱视和斜视中研究代谢活性的模式，以及在V2区域的正常受试者中，这是一个专门用于视觉处理的皮质区域。在特定的目标＃2中，连接将从猕猴中的眼部优势柱到区域V2。假设是，从被剥夺的眼睛的眼部优势柱中从细胞到V2区域的投影丧失是弱视的不重要因素，因为它可以防止视觉信息正常传递给高等中心。在特定的目标＃3中，将检查负责视觉抑制的神经机制。在斜视中，儿童无法保持眼睛正常的对准。他们通过从一只眼睛抑制图像来避免双视力。如何通过测试其视觉功能和眼部固定偏好来研究这种情况。二分法将用于绘制视野中的视觉抑制模式。这些心理物理测试完成后，每只眼睛之间来回切换固定时，记录将由单个细胞制成。目标是确定细胞的发射速率如何通过视觉抑制调节。面向同类和交叉的光栅将用于搜索双眼促进和抑制，并测试这些效果是否取决于哪种眼睛在感知上占主导地位。最后，视野中区域抑制的区域将与眼部优势柱中的CO活性模式相关。假设是，在被抑制的眼睛的色谱柱中，代谢活性将减少。这些实验从弱视和斜视的结构基础中进行的新见解可能会改善预防和治疗这些疾病的方法。