Quantitative Fundus Autofluorescence in Retinal Disorders

视网膜疾病中的定量眼底自发荧光

• 批准号: 9084593
• 负责人: Janet Ruthe Sparrow
• 金额: $ 45.47万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9084593
• 关键词: Address; Affect; Age; Age related macular degeneration; Alleles; Biological; Carrier State; Cells; Chemicals; Clinical; Complex; Complex Mixtures; Data; Deposition; Diagnosis; Disease; Disease Progression; Epithelial; Ethnic Origin; Etiology; Exhibits; Eye; Flecks; Fundus; Gender; Genetic; Genotype; Health; Image; Individual; Influentials; Investigation; Lasers; Legal Blindness; Light; Link; Lipofuscin; Longitudinal Studies; Measurement; Measures; Methods; Monitor; Mutation; Normal Range; Ophthalmoscopy; Optics; Participant; Pathogenesis; Patients; Pattern; Phagocytosis; Phenotype; Photoreceptors; Physics; Pigments; Positioning Attribute; Process; Research Personnel; Retina; Retinal; Retinal Degeneration; Retinal Diseases; Retinal Pigments; Retinaldehyde; Retinitis Pigmentosa; Scanning; Sparrows; Stargardt' s disease; Structure of retinal pigment epithelium; Susceptibility Gene; Testing; Variant; Work; aged; base; clinical phenotype; cohort; early onset; fluorophore; follow-up; human disease; macular dystrophy; pattern dystrophies; risk variant; therapy outcome

DESCRIPTION (provided by applicant): The inherent autofluorescence (AF) of the fundus originates from RPE lipofuscin. While RPE lipofuscin is amassed even in healthy eyes, homozygous mutations in ABCA4 are well known to confer accelerated formation of these fluorophores. Moreover, imaging of fundus AF by confocal scanning laser ophthalmoscopy (cSLO) has shown that the patterns and intensities of AF deviate from normal in several retinal disorders. Thus we aim to demonstrate that a standardized approach to quantifying fundus AF (qAF) can assist in the diagnosis of retinal disease, in the monitoring of disease progression and in the assessment of therapeutic outcomes. To enable this investigation we have gathered normative qAF data from a large number of participants with healthy eye status (aged 6-60) so as to establish ranges of qAF values with respect to age, gender and ethnicity. Going forward we will use these normal values to examine for genotype/phenotype correlations between specific ABCA4 alleles and fundus AF levels (qAF) in patients diagnosed with ABCA4- associated disease (Aim 1.1). In longitudinal studies we will measure changes in qAF values after 1 and 2 year follow-up of ABCA4-affected individuals (Aim 1.2). We will determine whether the carrier state (heterozygous) of ABCA4 is associated with elevated RPE lipofuscin, the latter being measured as qAF and compared to age-matched normals (Aim 1.3). We will also investigate the cellular basis of retinal flecks (Aim 1.4). In Aim 2, we will determine whether the quantification of fundus SW-AF can aid in differentiating between pattern dystrophy (PD) associated with PRPH2/RDS mutations versus similar phenotypes observed with ABCA4 variants (Aim 2.1). We will also compare qAF values in individuals presenting with bull's eye macular dystrophy that is of ABCA4- versus non-ABCA4 origin (Aim 2.2). In patients with RP, we will measure qAF over the autofluorescent rings that are often a feature of this disorder. qAF Intensities inside, within and outside the rings will be compared to levels in our normal controls so as to further the use of fundus AF imaging to monitor disease progression in RP. In Aim 4, we will determine whether elevated fundus AF is a factor influencing the onset and progression of AMD when controlling for specific CFH and ARMS2 alleles. In summary, the studies proposed in this application will examine the contribution that the lipofuscin of retina makes to the onset and progression of several retinal diseases and will demonstrate that quantitation of fundus AF facilitates the diagnosis and monitoring of some retinal disorders.

描述（申请人提供）：眼底固有的自发荧光（AF）源自RPE脂褐素。虽然 RPE 脂褐素即使在健康的眼睛中也会积聚，但众所周知，ABCA4 的纯合突变会加速这些荧光团的形成。此外，通过共焦扫描激光检眼镜 (cSLO) 进行的眼底 AF 成像显示，在几种视网膜疾病中，AF 的模式和强度偏离正常。因此，我们的目标是证明量化眼底 AF (qAF) 的标准化方法可以帮助诊断视网膜疾病、监测疾病进展和评估治疗结果。为了进行这项调查，我们从大量眼睛健康的参与者（6-60 岁）收集了规范的 qAF 数据，以便确定年龄、性别和种族的 qAF 值范围。展望未来，我们将使用这些正常值来检查诊断为 ABCA4 相关疾病的患者中特定 ABCA4 等位基因与眼底 AF 水平 (qAF) 之间的基因型/表型相关性（目标 1.1）。在纵向研究中，我们将测量受 ABCA4 影响的个体 1 和 2 年随访后 qAF 值的变化（目标 1.2）。我们将确定 ABCA4 的携带状态（杂合）是否与 RPE 脂褐素升高相关，后者以 qAF 进行测量，并与年龄匹配的正常值进行比较（目标 1.3）。我们还将研究视网膜斑点的细胞基础（目标 1.4）。在目标 2 中，我们将确定是否 眼底 SW-AF 的量化有助于区分与 PRPH2/RDS 突变相关的模式营养不良 (PD) 与 ABCA4 变异体观察到的类似表型（目标 2.1）。我们还将比较 ABCA4 来源与非 ABCA4 来源的牛眼黄斑营养不良个体的 qAF 值（目标 2.2）。对于 RP 患者，我们将测量自发荧光环上的 qAF，这通常是这种疾病的一个特征。将环内、环内和环外的 qAF 强度与我们正常对照的水平进行比较，以便进一步使用眼底 AF 成像来监测 RP 的疾病进展。在目标 4 中，我们将在控制特定 CFH 和 ARMS2 等位基因时确定升高的眼底 AF 是否是影响 AMD 发病和进展的因素。总之，本申请中提出的研究将检验视网膜脂褐质对多种视网膜疾病的发生和进展的贡献，并将证明眼底AF的定量有助于某些视网膜疾病的诊断和监测。