MECHANISMS OF OCULAR DEVELOPMENT

眼睛发育的机制

• 批准号: 6178664
• 负责人: THOMAS T NORTON
• 金额: $ 32.78万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6178664
• 关键词: Scandentia; biochemistry; collagen; extracellular matrix; eye accommodation; gene expression; growth /development; human tissue; metalloendopeptidases; myopia; neural information processing; neuroregulation; protein biosynthesis; proteoglycan; sclera; visual feedback; visual perception; visual stimulus

The goal of this project is to understand the visually-guided regulation of axial length in juvenile eyes. Evidence from animal models strongly suggests that visual signals are used to match the developing eye s length to its optical power to produce eyes that are in good focus (e.g., the eyes become emmetropic.) Some aspects of the visual images on the retina, such as the amount of hyperopic defocus, stimulates eyes to elongate. As young eyes move from hyperopia toward emmetropia, the visual stimulus for elongation is reduced and the axial elongation rate is slowed, keeping the retina in the focal plane. Visual/neural control of scleral extensibility may be a key component in regulating the elongation rate of mammalian eyes during emmetropization. Our studies in tree shrews (small mammals closely related to primates) have found that the extensibility of the sclera is regulated by the visual environment. The sclera becomes more extensible in eyes with an environmentally-induced increase in elongation rate and less extensible in eyes with a decreased elongation rate. A detailed understanding of the spatial location and temporal pattern of changes within the sclera is needed to 1) determine how specific changes in scleral components produce changes in extensibility, and 2) help define the latency and signaling pathway(s) by which signals of retinal origin reach the sclera via the choroid. There are two broad objectives for this project period: First, Specific Aim 1 is to better define the visual stimuli that increase and decrease axial elongation rate. This will be accomplished by manipulating and measuring the amount and sign of defocus during the development of induced myopia. Second, Specific Aims 2 and 3 are to understand in detail the remodeling of the scleral matrix that controls axial elongation, learning what changes, where the changes occur and when the changes occur relative to changes in the visual environment and changes in axial elongation. Specific Aim 2 is to define and localize the specific changes in collagen and proteoglycans in the scleral extracellular matrix that occur during the development of induced myopia and during recovery from an induced myopia; Specific Aim 3 is to measure the time-course and latency of changes in scleral fibroblast gene expression for synthesis and degradation of scleral extracellular matrix during the development of induced myopia and recovery. The proposed experiments will significantly advance our understanding of the mammalian emmetropization mechanism. This, in turn, will help us to learn how human eyes normally control their elongation, and how interactions with the visual environment can lead to myopia (nearsightedness) in children.

该项目的目的是了解少年眼中轴向长度的视觉指导调节。 来自动物模型的证据强烈表明，视觉信号用于将发育中的眼睛长度与其光学能力相匹配，以产生良好的眼睛（例如，眼睛变成杂志。）视网膜上视觉图像的某些方面，例如触及散热器的数量，可以刺激眼睛刺激眼睛。 随着年轻的眼睛从远视向艾米特罗尼亚移动，延伸的视觉刺激减少了，轴向伸长速率变慢，使视网膜保持在焦平面。 巩膜可扩展性的视觉/神经控制可能是调节润肤过程中哺乳动物眼睛伸长率的关键组成部分。 我们在树sh的研究（与灵长类动物密切相关的小型哺乳动物）发现，巩膜的可扩展性受视觉环境的调节。 巩膜在眼睛中变得更加可扩展，而环境引起的伸长率的增加，而在伸长率降低的眼睛中，眼睛的伸长率较低。 需要详细了解巩膜内的空间位置和变化的时间模式。该项目期间有两个广泛的目标：首先，特定目标1是更好地定义增加和降低轴向伸长率的视觉刺激。 这将通过在诱发近视的发展过程中操纵和测量散焦的数量和迹象来实现。 其次，具体目的2和3是要详细了解控制轴向伸长的硬化矩阵的重塑，了解什么变化，发生变化的地方以及相对于视觉环境的变化以及轴向伸长的变化发生的变化时发生的变化。 具体目的2是在诱导的近视发育过程中以及从诱导的近视中恢复期间发生的硬化细胞外基质中胶原蛋白和蛋白聚糖的特定变化；具体目的3是在诱导的近视和恢复过程中衡量巩膜成纤维细胞基因表达变化的时间顺序和延迟，以使硬化细胞外基质的合成和降解。提出的实验将显着提高我们对哺乳动物弹性化机制的理解。反过来，这将有助于我们了解人类的眼睛通常如何控制其伸长率，以及与视觉环境的互动如何导致儿童的近视（近视）。