Genotype phenotype associations in inherited retinal degeneration

摘要 这是一份K99/R00 NIH独立之路奖的申请表。我是哈佛大学的博士后研究员 西南部的视网膜基金会。在我的赞助人大卫·伯奇博士的帮助下，我正在建立 作为一名年轻的研究人员，我从事遗传性视网膜疾病的临床研究。这个K99奖将为我提供 在必要的支持下完成以下目标：(1)熟练地进行视网膜检查 视网膜色素变性患者的结构；(2)成为患者检测技能和方法的专家； (3)对心理物理学的理论理解。为了实现这一点，我收集了一份建议 团队由主要赞助商、科学总监伯奇博士组成，他进行以患者为导向的研究 遗传性眼病和3位顾问：兰德·斯宾塞博士，德克萨斯视网膜协会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；Donald Hood博士，他是 一位光传导级联的数学建模专家，擅长视网膜疾病和 临床测试。 视网膜色素性视网膜炎的特点是视网膜变性，主要影响视杆状感光细胞。我的 研究的重点是测量已知遗传基因的视网膜色素变性患者的视杆功能。 突变以寻找周边视网膜视杆状视野丧失的模式(目标1)并比较这一新发现 用传统的杆功能指标评价杆功能的方法(目标2)。最后，比较研究。 将进行具有心理物理测试的解剖特征(目标3)。我将使用现有的西南航空。 西南视网膜基金会的眼睛注册表数据库，以登记和跟踪退行性变化 已知基因突变的50例视网膜色素变性患者。在目标1中，我将确定一个新的- 发展的大视野、暗适应、双色视野是可靠的，如果RP患者有独特的视杆-视网膜 介导性视野丧失。目标2将确定最敏感和最可靠的监测棒功能的方法 随着时间的推移，视网膜色素变性和AIM 3将光感受器功能与相应的位置联系起来 视网膜结构。这项研究将为未来杆函数的测量奠定基础，并将产生数据 这笔资金将用于R00奖励结束前的RO1奖励申请。

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.