Mechanisms underlying emmetropization and local eye growth regulation

正视化和局部眼睛生长调节的机制

基本信息

批准号：
7616263
负责人：
CHRISTINE FRANCES WILDSOET
金额：
$ 33.84万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-01-01 至 2013-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7616263
关键词：
Accounting Address Adverse effects Affect Amacrine Cells Anatomy Animals Astigmatism Back Behavior Biological Assay Biomechanics Birds Birth Cavia Cell Culture Techniques Childhood Choroid Clinical Clinical Trials Contact Lenses Cornea Data Development Distant Dopamine Effectiveness Epidemic Exhibits Exposure to Eye Eyeglasses Failure Figs - dietary Financial compensation Gene Expression Genes Genetic Glucagon Growth Growth Factor Homeostasis Human Hyperopia Image In Vitro Ions Lead Left Length Light Link Literature Mammals Modeling Molecular Molecular Biology Molecular Profiling Myopia Nerve Neurotransmitters Nutrient Operative Surgical Procedures Optics Pathology Pattern Peripheral Pharmaceutical Preparations Pharmacological Treatment Pharmacology Photoreceptors Physiology Play Population Predisposition Prevalence Primates Process Property Pupil Recycling Refractive Errors Regulation Relative (related person)Research Research Design Retina Retinal Retinoids Role Sclera Shapes Signal Pathway Signal Transduction Site Source Stimulus Structure of retinal pigment epithelium Techniques Testing Tissues United States National Institutes of Health Vision Visual Waste Products Water Work analog cell type congenital cataract deprivation design effective therapy emmetropization experience falls image processing improved in vivo interest lens macula macular edema neovascularization novel prevent public health relevance receptor research study response theories tool vision development

项目摘要

DESCRIPTION (provided by applicant): Emmetropization is the regulatory process that matches the eye's length to its optical power, bringing distant objects to focus on the retina with accommodation relaxed. Myopia, or shortsightedness, is the failure of emmetropization in which the eye grows too long for its optical power. Myopia's association with sight-threatening complications, and near-epidemic prevalence in several populations, make it critical to understand the determinants of emmetropization, without which effective treatments are unlikely to be developed. The chick eye has provided a very fruitful model of emmetropization, clarifying the optical conditions that lead to myopia, providing evidence for local retinal control of eye growth, and identifying optical manipulations that inhibit eye elongation, which are therefore potential myopia treatments. Aims and Studies: (1) We will study local molecular signaling across the retinal pigment epithelium (RPE), which separates the image-processing retina from the choroid and eye shape-determining sclera, using molecular techniques to delineate patterns of gene expression in eyes undergoing experimentally altered growth through exposure to myopic and hyperopic defocus, and in cultured RPE treated with presumptive retinal growth modulators. We will then conduct in vivo tests of growth factors identified in gene expression studies. (2) We will use these genetic signatures, in combination with drugs known from previous work to modulate responses to imposed myopia and hyperopia, to study the mechanisms of eye growth induced by simultaneous, competing myopic and hyperopic defocus produced by several types of multifocal and astigmatic lenses. We will evaluate hypotheses regarding retinal processing, optical aberrations, and peripheral retinal growth to explain lens effects. (3) We will develop a guinea pig model to extend our findings on local ocular growth regulation to mammalian eyes, and to compare mammalian and avian responses to simple and competing defocus stimuli. PUBLIC HEALTH RELEVANCE Emmetropization is the regulatory process that matches the eye's length to its optical power, bringing distant objects to focus on the retina with accommodation relaxed. Myopia, or shortsightedness, represents the failure of emmetropization in which the eye grows too long for its optical power, in near-epidemic prevalence in several populations, with associated sight-threatening complications, making it critical to understand the determinants of emmetropization, without which effective treatments are unlikely to be developed. This project will apply modern molecular biology and optical techniques to investigate the mechanisms underlying emmetropization, with a view to developing novel treatments for myopia.

描述（由申请人提供）：Emetropization是将眼睛长度与其光学功率相匹配的调节过程，使遥远的物体可以放松身心。近视或近视性是弹性化的失败，其中眼睛的光功率太长。近视与威胁视力并发症以及几个人群中几乎流动的患病率的关联，使了解弹性化的决定因素至关重要，没有这些决定因素，就不太可能开发出有效的治疗方法。雏鸡的眼睛提供了一种非常富有成果的弹性化模型，阐明了导致近视的光学条件，提供了局部视网膜对眼睛生长的视网膜控制的证据，并确定了抑制眼睛伸长的光学操纵，因此，这是潜在的近视治疗。目的和研究：（1）我们将研究整个视网膜色素上皮（RPE）的局部分子信号，将图像处理的视网膜与脉络膜和眼睛形状确定的巩膜分开，使用分子技术，使用分子技术来描述通过经过实验性变化的基因表达，并与我匹配的经历相反，并在我眼前进行了反应，并在肌液中进行了多种变化，并在肌液中进行了多种变化。视网膜生长调节剂。然后，我们将对基因表达研究中确定的生长因子进行体内测试。（2）我们将使用这些遗传信号，结合以前工作已知的药物来调节对强加的近视和远视的反应，以研究由几种类型的多焦点和敏捷镜头产生的同时，竞争性近视和近视型诱导的眼睛生长机制。我们将评估有关视网膜加工，光学畸变和周围视网膜生长的假设，以解释晶状体效应。（3）我们将开发一个豚鼠模型，以将我们对局部眼生长调节的发现扩展到哺乳动物的眼睛，并将哺乳动物和鸟类的反应与简单且竞争的液化刺激进行比较。公共卫生相关性Emetropization是一个调节过程，将眼睛的长度与其光功能相匹配，使远处的物体放松地将遥远的物体专注于视网膜上。近视或短视性代表了弹性化的失败，在几个人群中，眼睛的光学能力过长，其光学能力太长，并且存在相关的视力危险并发症，这使得了解润肤量的决定因素至关重要，而无需开发有效的治疗方法就无法开发出来。该项目将采用现代分子生物学和光学技术来研究弹性化的基本机制，以期为近视开发新的治疗方法。