Adaptive Optics Fluorescence Lifetime Ophthalmoscopy (AOFLIO) in healthy people and with disease

项目摘要 视网膜色素上皮(RPE)是维持人的健康和正常功能的关键 光感受器，因此与许多导致失明的视网膜疾病有关。贯穿始终 在生命中，RPE细胞积累的废物聚集成荧光脂褐素颗粒。在斯塔加特 疾病时，有加速脂褐素蓄积和分子组成变化的现象 脂褐素颗粒。脂褐素的荧光使可视化马赛克成为可能 使用自适应光学扫描光检眼镜的RPE细胞。然而，RPE细胞的特征 仅从结构和强度不能提供关于细胞健康的足够信息。 RPE发出的荧光的时间延迟的测量与RPE的性质有关 荧光团及其环境，包括脂褐素的组成。自适应的发展 人RPE马赛克的光学荧光终身眼底检查(AOFLIO)将提供一种 重要的工具，以表征RPE细胞在健康和疾病的眼睛，其中结构和 功能性生物标记物可用于RPE评估，以及诊断和监测疾病。 该提案旨在开发和建立AOFLIO检测细胞水平变化的能力 与健康衰老和Stargardt病有关的黄斑。荧光寿命将为 通过比较20岁至20岁成人受试者的AOFLIO来测量整个视网膜 70年了。Stargardt患者识别RPE层荧光寿命变化的能力 疾病(10-30年)和超过3年的进展将通过纵向AOFLIO进行评估 在萎缩区域、移行区和临床正常的视网膜上进行测量。其中一些 这些受试者还将用广域荧光寿命成像的临床原型进行成像。 眼底镜(Flio)，生成独一无二的比较数据。此外，目前的AOFLIO 仪器将被旨在提高光效的创新新技术所取代 并解析出比目前可能的更精细的特征。该项目旨在评估以下项目的性能 AOFLIO，为我们未来的调查做好准备，以建立AOFLIO作为 视网膜退行性疾病的生物标志物，将AOFLIO确立为用于 通过对潜在新疗法的效果提供快速反馈，进行临床试验。

Project Summary The retinal pigment epithelium (RPE) is critical to maintaining the health and normal function of photoreceptors, and is therefore involved in many retinal diseases that cause blindness. Throughout life, RPE cells accumulate waste products that cluster into fluorescent lipofuscin granules. In Stargardt disease, there is an acceleration of lipofuscin accumulation and changes in the molecular composition of the lipofuscin granules. The fluorescence of lipofuscin makes it possible to visualize the mosaic of RPE cells with an adaptive optics scanning light ophthalmoscope. However, characterizing RPE cells from structure and intensity alone does not provide sufficient information about the health of the cells. Measurement of the time delay in fluorescence emitted from RPE is related to the nature of the fluorophores and their environment including the composition of lipofuscin. Development of adaptive optics fluorescence lifetime ophthalmoscopy (AOFLIO) of the human RPE mosaic will provide an important tool to characterize RPE cells in both healthy and diseased eyes, where structural and functional biomarkers may be used for RPE evaluation, as well as diagnosing and monitoring disease. This proposal aims to develop and establish the ability of AOFLIO to detect cellular-level changes across the macula associated with healthy aging and Stargardt disease. Fluorescence lifetime will be measured across the retina by comparing AOFLIO in adult human subjects ranging in age from 20 to 70 years. The ability to identify RPE layer fluorescence lifetime changes in patients with Stargardt disease (10-30 years) and progression over 3 years will be assessed by longitudinal AOFLIO measurements in regions of atrophy, at the transition zone and in clinically-normal retina. Some of these subjects will also be imaged with a clinical prototype for widefield fluorescence lifetime imaging ophthalmoscopy (FLIO), generating one-of-a-kind comparative data. In addition, the current AOFLIO instrumentation will be replaced with innovative new technology designed to improve light efficiency and resolve finer features than currently possible. This project aims to evaluate the performance of AOFLIO, preparing us for future investigations to establish AOFLIO as an important measure of biomarkers of retinal degenerative disease, establishing AOFLIO as a prospective endpoint for use in clinical trials by providing rapid feedback on the effects of potential new therapies.