Quantitative Fundus Autofluorescence in Retinal Disorders

描述（由申请人提供）：眼底固有的自体荧光（AF）来源于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，通过共聚焦扫描激光眼底镜（cSLO）成像显示，在一些视网膜疾病中，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）那里收集了标准的qAF数据，以便建立与年龄、性别和种族有关的qAF值范围。接下来，我们将使用这些正常值来检测ABCA4相关疾病患者中特定ABCA4等位基因与眼底房颤水平（qAF）之间的基因型/表型相关性（Aim 1.1）。在纵向研究中，我们将测量abca4影响个体随访1年和2年后qAF值的变化（Aim 1.2）。我们将确定ABCA4的载体状态（杂合）是否与RPE脂褐素升高有关，后者以qAF测量，并与年龄匹配的正常人进行比较（Aim 1.3）。我们还将研究视网膜斑点的细胞基础（Aim 1.4）。在目标2中，我们将确定

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.