Clinical and Genetic Analysis of Retinopathy of Prematurity

描述(申请人提供)：本项目的长期目标是确定早产儿视网膜病变(ROP)发育的临床和遗传特征，并分析它们之间的关系。尽管生物医学研究数据正在以巨大的速度产生，但在整合从基因组学到成像再到临床医学的不同科学发现方面所做的工作要少得多。我们的总体假设是，遗传因素参与了ROP发病机制的启动和调控，ROP的临床、影像和遗传学表现之间存在病因学联系。这些假设将通过两个连续的特定目标进行检验：(1)从7个研究中心的1460多名有ROP风险的早产儿队列中招募、表型和收集遗传物质。数据将存储在将为该项目开发的基于网络的数据管理系统中。将充分了解三次系列眼底镜检查的人口学和临床特征，并捕获连续的广角图像。DNA将被分离出来，并准备用于基因分型。(2)利用计算机图像分析技术对视网膜血管特征进行量化，分析ROP临床表现与影像表现之间的关系。将评估综合量化影像特征、临床特征和环境风险因素对ROP易感性的影响的模型。在这个项目的竞争性更新期间，将进行基因分型、基因分析、根据需要招募更多的受试者以及临床和遗传特征的建模。最终，这些研究将提高对ROP和相关眼部疾病中新生血管形成以及婴儿正常血管发育的理解。此外，这项工作应该展示一个结合了基因和表型数据的健康信息管理原型。该项目将由具有临床眼科、生物医学信息学、遗传分析和统计遗传学专业知识的合作研究人员组成的多学科团队执行。 公共卫生相关性：在美国和全世界，ROP是导致儿童失明的主要原因，随着早产率的上升，面临疾病风险的婴儿数量正在增加。与视网膜血管发育和血管生成相关的快速进行性变化可以通过临床检查可视化，通过广角成像捕获，并进行遗传学分析。这一项目的发现将提高我们对ROP和其他新生血管疾病的发病机制的理解，并为识别哪些婴儿具有最高的疾病风险提供了更好的方法。

DESCRIPTION (provided by applicant): The long-term goal of this project is to identify clinical and genetic features of retinopathy of prematurity (ROP) development, and to analyze their relationships. Although biomedical research data are being generated at an enormous pace, much less work has been done to integrate disparate scientific findings across the spectrum from genomics to imaging to clinical medicine. Our overall hypotheses are that genetic factors are involved in the initiation and modulation of ROP pathogenesis, and that there are etiological relationships among clinical, imaging, and genetic findings in ROP. These hypotheses will be tested using two sequential Specific Aims: (1) Recruit, phenotype, and collect genetic material from a cohort of over 1460 premature infants at- risk for ROP from 7 study centers. Data will be stored in a web-based data management system that will be developed for this project. Demographic and clinical features from three serial ophthalmoscopic examinations will be ascertained fully, and serial wide- angle images will be captured. DNA will be isolated and prepared for genotyping. (2) Quantify retinal vascular features using computer-based image analysis, and analyze relationships between clinical and image findings in ROP. Models for integrating the effects of quantitative image traits, clinical features, and environmental risk factors on ROP susceptibility will be estimated. Genotyping, genetic analysis, recruitment of additional subjects as needed, and modeling of clinical and genetic traits will be pursued during competitive renewal of this project. Ultimately, these studies should improve understanding of neovascularization in ROP and related ocular diseases, and of normal vascular development in infants. In addition, this work should demonstrate a prototype for health information management which combines genotypic and phenotypic data. This project will be performed by a multi-disciplinary team of collaborative investigators with expertise in clinical ophthalmology, biomedical informatics, genetic analysis, and statistical genetics. PUBLIC HEALTH RELEVANCE: ROP is a leading cause of childhood blindness in the United States and throughout the world, and the number of infants at risk for disease is increasing as the rate of premature birth rises. Rapidly-progressive changes associated with retinal vascular development and angiogenesis may be visualized by clinical examination, captured by wide-angle imaging, and analyzed genetically. Findings from this project should improve our understanding of the pathogenesis of ROP and other neovascular diseases, and provide better methods for identifying infants who are at highest risk of developing disease.