STRUCTURAL BASIS OF AMBLYOPIA

弱视导致视力丧失的2%的美国人口，尽管 提高检测和治疗标准。 其广泛目标 这一建议的目的是阐明弱视的结构基础， 人类 几乎没有直接的信息是关于病理的 弱视引起的人类视觉皮层的变化，部分原因是 大多数针对动物的侵入性实验技术 研究不能用于人类。 细胞色素氧化酶（CO）法 Wong-Riley模型的特殊优点是适合于制图 人体尸检组织中的代谢活动模式 在这 建议，CO组织化学将适用于标本的视觉 从有早期脑梗死病史的患者尸检中获得的皮质 视力丧失 具体目标是确定 眼优势柱可塑性的关键期， 检查涉及视觉功能丧失（或实际丧失）的病例 一只眼睛，例如，视网膜母细胞瘤，创伤），在不同年龄， 童年. 此外，纹状皮质中的CO活性模式 与不同形式的弱视相关的测试将由 检查患者的标本， 早期单侧白内障、斜视或屈光参差。 CO还将 用于确定人类新生儿中是否存在贴片。 解释人体组织中的CO数据，并进一步探索 视觉皮层的结构和生理变化 对弱视进行一系列相关实验 在猕猴身上。 具体目标是：1）确定是否存在 梯度存在于视野的皮层表示上， 从中央凹到周边，在眼优势的易感性 柱收缩引起的视觉剥夺。 这将是 通过重建眼优势的整个马赛克来实现 柱，用CO组织化学和脯氨酸放射自显影标记， 在不同年龄的单侧眼睑缝合剥夺的猴子中。（二） 确定猕猴的眼优势柱是否 一出生就被隔离 这将通过眼内注射来实现 [3 H]-脯氨酸在剖腹产前1周的猴中的含量 正常妊娠的结束。3)来描述感受野的特征 中央凹内细胞的特性和眼优势 代表性的弱视猴子。 这将通过使用 定量电生理记录技术。4)以确定 视觉剥夺是否减少丘脑对V1区CO斑的输入 为弱视的眼睛服务。 这将通过以下方式实现： [3 H]-脯氨酸注射到丘脑视觉剥夺 猴子在V1中标记贴片。5)以确定是否视觉 剥夺导致V1 -> V2投射的选择性丧失， 为被剥夺的眼睛服务。 这将通过注射辣根来实现 过氧化物酶转化为V2，并将其位置与逆行 V1区标记细胞，眼优势柱标记为CO 组织化学

Amblyopia causes visual loss in 2% of the American population, despite improved standards for detection and treatment. The broad objective of this proposal is to elucidate the structural basis of amblyopia in humans. Little direct information is available about the pathological changes induced by amblyopia in human visual cortex, in part because most of the invasive experimental techniques developed for animal studies cannot be used in humans. The cytochrome oxidase (CO) method of Wong-Riley has the special advantage that it is suitable for mapping patterns of metabolic activity in human autopsy tissues. In this proposal, CO histochemistry will be applied to specimens of visual cortex obtained post-mortem from patients with a history of early visual loss. The specific aim is to define the timing and duration of the critical period for the plasticity of ocular dominance columns, by examining cases involving loss of visual function (or actual loss of one eye, e.g., retinoblastoma, trauma) at various ages during childhood. In addition, the patterns of CO activity in striate cortex associated with different forms of amblyopia will be tested by examining specimens from patients with well-documented histories of early unilateral cataract, strabismus, or anisometropia. CO will also be used to determine if patches are present in human newborns. To interpret the CO data from human tissues, and to further explore the structural and physiological alterations in visual cortex responsible for amblyopia, a series of correlative experiments will be performed in macaque monkeys. The specific aims are: 1) To determine whether a gradient exists across the cortical representation of the visual field, from fovea to periphery, in the susceptibility of ocular dominance columns to shrinkage induced by visual deprivation. This will be achieved by reconstructing the entire mosaic of ocular dominance columns, labelled with CO histochemistry and proline autoradiography, in monkeys deprived at different ages by unilateral eyelid suture. 2) To determine whether ocular dominance columns in macaques are segregated at birth. This will be achieved by intraocular injection of [3H]-proline in monkeys delivered by Caesarean section 1 week before the end of normal gestation. 3) To characterize the receptive field properties and ocular dominance of cells within the foveal representation of amblyopic monkeys. This will be achieved by using quantitative electrophysiological recording techniques. 4) To determine whether visual deprivation reduces thalamic input to CO patches in V1 serving the amblyopic eye. This will be achieved by making large injections of [3H]-proline into the thalamus of visually deprived monkeys to label the patches in V1. 5) To determine whether visual deprivation causes a selective loss of projections from V1 -> V2 which serve the deprived eye. This will be achieved by injecting horseradish peroxidase into V2, and correlating the position of retrogradely labelled cells in V1 with the ocular dominance columns labelled by CO histochemistry.