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 K99/R00 NIH 独立之路奖的申请。我是一名博士后研究员 西南视网膜基金会。在我的赞助商 David Birch 博士的帮助下，我正在建立 我自己是一名年轻的研究者，从事遗传性视网膜疾病的临床研究。这个K99奖将为我提供 获得实现以下目标所需的支持：（1）精通视网膜检查 色素性视网膜炎患者的结构； (2) 成为患者检测技能和方法方面的专家； (3)获得心理物理学的理论理解。为了实现这一目标，我整理了一份咨询 团队由主要发起人、科学总监 Birch 博士组成，他进行了以患者为导向的研究 遗传性眼病和 3 名顾问：Rand Spencer 博士，Texas Retina Associates 的玻璃体视网膜专家； Joost Felius博士，生物统计分析和计算机编程专家；和唐纳德·胡德博士，他是 光转导级联数学建模专家，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主要影响视杆细胞的视网膜变性。我的 研究将重点测量患有已知遗传性视网膜色素变性的患者的视杆功能 突变来寻找周边视网膜中视杆视野丧失的模式（目标 1）并与该小说进行比较 使用传统的杆功能测量来评估杆功能的方法（目标 2）。最后，研究比较 将进行解剖学特征和心理物理测试（目标 3）。我将使用现有的西南 西南视网膜基金会的眼部登记数据库，用于登记和跟踪退行性变化 50 名患有已知基因突变的色素性视网膜炎患者。在目标 1 中，我将确定是否有新的—— 开发的宽视场、暗适应、双色视野是可靠的，如果 RP 患者具有独特的视杆细胞 介导的视野丧失。目标 2 将确定监测棒功能的最灵敏、最可靠的方法 随着时间的推移，视网膜色素变性和目标 3 将把光感受器功能与相应的位置联系起来。 视网膜结构。这项研究将构成未来杆功能测量的基础，并将生成数据 将在 R00 奖励结束前用于 RO1 补助金申请。