Genotype phenotype associations in inherited retinal degeneration

遗传性视网膜变性的基因型表型关联

• 批准号: 9771063
• 负责人: Lea D Bennett
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9771063
• 关键词: Advisory Committees; Affect; Anatomy; Application procedure; Applications Grants; Area; Award; Betula Genus; Biometry; Blindness; Clinical; Clinical Research; Clinical Trials; Color; Cone; Custom; Cystoid Macular Edema; DNA Sequence Alteration; Data; Databases; Defect; Degenerative Disorder; Detection; Devices; Disease; Doctor of Philosophy; Early Diagnosis; Early treatment; Electroretinography; Enrollment; Eye; Eye diseases; Floor; Foundations; Functional disorder; Fundus; Future; Genetic; Genotype; Goals; Image; Inherited; Laboratories; Lead; Light; Location; Maps; Measures; Mediating; Methodology; Methods; Monitor; Mutation; Optical Coherence Tomography; Outcome Measure; Pathway interactions; Patients; Pattern; Perimetry; Peripheral; Peripheral Scotomas; Phenotype; Photoreceptors; Phototransduction; Postdoctoral Fellow; Prevention; Procedures; Psychophysics; Records; Registries; Research; Research Personnel; Research Proposals; Retina; Retinal; Retinal Degeneration; Retinal Diseases; Retinal blind spot; Retinitis Pigmentosa; Scotoma; Specialist; Standardization; Structure; Testing; Texas; Thick; Time; United States National Institutes of Health; Vertebrate Photoreceptors; Vision; Visual Fields; computer program; density; field study; follow-up; geographic atrophy; improved; inherited retinal degeneration; interest; light effects; light intensity; mathematical model; membrane-associated placental tissue protein 1; novel; outcome forecast; patient oriented research; patient subsets; photoreceptor degeneration; research clinical testing; response; retinal rods; skills

Abstract This is an application for a K99/R00 NIH Pathway to Independence award. I am a postdoctoral fellow at the Retina Foundation of the Southwest. With the help of my sponsor, David Birch, PhD, I am establishing myself as a young investigator in clinical research of inherited retinal disease. This K99 award will provide me with the support necessary to accomplish the following goals: (1) to become proficient at examination of retinal structure in people with retinitis pigmentosa; (2) to become an expert in patient testing skills and methodology; and (3) to obtain theoretical understanding of psychophysics. To achieve this, I have assembled an advisory team comprised of a primary sponsor, Dr. Birch, Scientific Director, who conducts patient-oriented research on genetic eye disease, and 3 advisors: Dr. Rand Spencer, a vitreo-retinal specialist at Texas Retina Associates; Dr. Joost Felius, an expert in biostatistical analysis and computer programming; and Dr. Donald Hood, who is an expert in mathematical modeling of the phototransduction cascade and specializes in retinal diseases and clinical testing. Retinitis pigmentosa is characterized by retinal degeneration primarily affecting rod photoreceptors. My research will focus on measuring rod function in patients with retinitis pigmentosa who have known genetic mutations to look for patterns of rod visual field loss in the peripheral retina (Aim 1) and compare this novel method of evaluating rod function with traditional measures of rod function (Aim 2). Finally, studies comparing anatomical features with psychophysical testing will be performed (Aim 3). I will use the existing Southwest Eye Registry database at the Retina Foundation of the Southwest to enroll and track degenerative changes in 50 patients with retinitis pigmentosa who have known genetic mutations. In Aim 1, I will determine if a newly- developed wide-field, dark-adapted, two-color perimeter is reliable and if patients with RP have distinctive rod- mediated visual field loss. Aim 2 will identify the most sensitive and reliable method of monitoring rod function over time in retinitis pigmentosa and Aim 3 will relate photoreceptor function with corresponding locations of retinal structure. This research will form the basis of future measures of rod function and will generate the data that will be used for an RO1 grant application before the end of the R00 award.

抽象的 这是获得独立奖的K99/R00 NIH途径的申请。我是博士后家伙 西南的视网膜基金会。在我的赞助商David Birch博士的帮助下，我正在建立 我自己是遗传性视网膜疾病临床研究的年轻研究者。这个K99奖将为我提供 在实现以下目标所需的支持下：（1）精通视网膜检查 色素性视网膜炎患者的结构； （2）成为患者测试技能和方法论专家； （3）获得对心理物理学的理论理解。为了实现这一目标，我已经组装了一个咨询 团队由主要赞助商，科学主任伯奇（Birch）博士组成，他对患者进行研究 遗传眼病和3名顾问：德克萨斯州视网膜协会的玻璃体视网膜专家兰德·斯宾塞（Rand Spencer）博士； 生物统计分析和计算机编程专家Joost Felius博士；还有唐纳德·胡德（Donald Hood）博士 光转导级联的数学建模专家，专门研究视网膜疾病和 临床测试。 色素性视网膜炎的特征是视网膜变性主要影响棒感光体。我的 研究将着重于测量知识遗传的视网膜炎患者的杆功能 突变以寻找周围视网膜中杆视野损失的模式（AIM 1）并比较这本小说 通过传统的杆功能测量评估杆功能的方法（AIM 2）。最后，研究比较 将进行心理物理测试的解剖学特征（AIM 3）。我将使用现有的西南 西南视网膜基金会的眼注册表数据库，以注册和跟踪变化的变化 有50例已知基因突变的视网膜炎患者。在AIM 1中，我将确定是否是新的 发达的宽场，深色适应的两色周长是可靠的，如果RP患者具有独特的杆 介导的视野损失。 AIM 2将确定监视杆功能最敏感和最可靠的方法 随着时间的流逝，色素和AIM 3的视网膜炎将与相应的位置相关 视网膜结构。这项研究将构成ROD功能未来度量的基础，并将生成数据 这将用于R00奖励结束之前的RO1赠款申请。