Molecular Characterization of Chick Retina during Refractive Development

鸡屈光发育过程中视网膜的分子特征

• 批准号: 7580653
• 负责人: RICHARD A STONE
• 金额: $ 43.49万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7580653
• 关键词: 3-Dimensional; Accounting; Biochemical; Biological; Biological Assay; Candidate Disease Gene; Cells; Chickens; Child; Choroid; Clinical Research; Core Facility; Data; Development; Etiology; Eye; Eyeglasses; Gene Expression; Gene Expression Profile; Genes; Genome; Goggles; Growth; Human; Image; In Situ Hybridization; Laboratories; Laboratory Research; Lead; Learning; Link; Measures; Mediating; Mediator of activation protein; Methods; Modeling; Molecular; Molecular Profiling; Myopia; Pathway interactions; Pattern; Pennsylvania; Pharmacology; Polymerase Chain Reaction; Process; Proteins; Protocols documentation; Public Health; Refractive Errors; Regulation; Research; Research Personnel; Resolution; Retina; Retinal; Reverse Transcription; Role; Sclera; Shapes; Signal Pathway; Signal Transduction; Spatial Distribution; Structure of retinal pigment epithelium; Study models; Testing; Time; Tissue-Specific Gene Expression; Universities; Vision; Vitreous Chamber; Work; base; deprivation; effective therapy; emmetropization; follow-up; genome-wide; in vivo; innovation; laser capture microdissection; lens; mRNA Expression; novel; prevent; product development; public health relevance; success; visual stimulus

DESCRIPTION (provided by applicant): Current research indicates that image blur or defocus alters eye growth and refraction and that the retina in large part governs these processes. However, a comprehensive understanding of the retinal signaling that accounts either for emmetropization (i.e., normal refraction) or for refractive errors has remained elusive, and clinically acceptable therapies that either prevent myopia onset or meaningfully slow its progression are unavailable. Despite major contributions to other fields, available molecular applications have not yet helped achieve a comprehensive mechanistic framework to understand the regulation of post-natal eye growth and refractive development. We hypothesize that visual stimuli altering eye growth induce transcriptome level changes in the retina and that these molecular signatures can identify important retinal mediators of refractive development. Our novel and far-reaching Preliminary Studies, defining retinal gene expression in form-deprivation myopia of chick, support this hypothesis. We propose transcriptome profiling of three established eye growth models in chick (concave spectacle lens, convex spectacle lens or goggle wear) and follow-up pharmacological and biochemical studies to establish potential roles in refractive development of the products of differentially regulated genes. Combining an interdisciplinary investigator team and core facilities at the University of Pennsylvania, we propose the following four inter-related Specific Aims: 1) identify differentially expressed retinal genes in lens-induced alterations of eye growth; 2) profile differential gene expression by retinal pigment epithelium (RPE) in visually altered eye growth; 3) establish the spatial distribution of differentially expressed retinal genes; and 4) characterize roles of the products of selected genes in eye growth regulation. We believe that our plan for transcriptome profiling and the related pharmacology will identify and characterize the molecular signaling by which the retina governs post-natal eye growth and refractive development. We anticipate that this work will generate novel and useful hypotheses that can be applied not only in the laboratory but also to the clinical study of refractive errors in children. We hope ultimately to stimulate the development of much needed, effective therapies to arrest myopia in children. PUBLIC HEALTH RELEVANCE: Despite the major public health impact, the etiologies of refractive errors generally and myopia in particular are poorly understood. We propose an innovative approach of evaluating altered gene expression in eyes of chicks developing refractive errors. Given past successes in applying findings in chick to human refractive development, we are optimistic that the proposed research will lead to novel ideas that can be used to understand and hopefully to treat the development of refractive errors in children.

描述（由申请人提供）：目前的研究表明，图像模糊或散焦会改变眼睛的生长和屈光，视网膜在很大程度上控制着这些过程。然而，对视网膜信号的全面理解，无论是正视化（即，正常屈光）或屈光不正的治疗仍然是难以捉摸的，并且临床上可接受的预防近视发作或有意义地减缓其进展的治疗是不可用的。尽管对其他领域做出了重大贡献，但可用的分子应用尚未帮助实现全面的机制框架，以了解出生后眼睛生长和屈光发育的调节。我们假设视觉刺激改变眼睛生长诱导视网膜中转录组水平的变化，这些分子特征可以识别屈光发育的重要视网膜介质。我们的新的和深远的初步研究，确定视网膜基因表达的形觉剥夺近视的小鸡，支持这一假设。我们建议转录组分析的三个已建立的眼睛生长模型在鸡（凹眼镜透镜，凸眼镜透镜或护目镜磨损）和后续的药理学和生化研究，以建立潜在的作用，屈光发展的差异调节基因的产品。本研究结合宾夕法尼亚大学的跨学科研究团队和核心设施，提出了以下四个相互关联的具体目标：1）鉴定晶状体诱导的眼生长改变中差异表达的视网膜基因; 2）描述视觉改变的眼生长中视网膜色素上皮（RPE）的差异基因表达; 3）建立差异表达的视网膜基因的空间分布;和4）表征所选基因的产物在眼睛生长调节中的作用。我们相信，我们的转录组分析和相关药理学计划将确定和表征视网膜控制出生后眼睛生长和屈光发育的分子信号传导。我们预计这项工作将产生新颖且有用的假设，这些假设不仅可以应用于实验室，还可以应用于儿童屈光不正的临床研究。我们希望最终能够刺激急需的有效疗法的发展，以阻止儿童近视。公共卫生相关性：尽管对公众健康有重大影响，但人们对屈光不正的病因，特别是近视的病因知之甚少。我们提出了一种创新的方法来评估改变基因表达的小鸡发展屈光不正的眼睛。鉴于过去成功地将小鸡的发现应用于人类屈光发育，我们乐观地认为，拟议的研究将产生新的想法，可用于理解并有望治疗儿童屈光不正的发展。