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

健康人和疾病患者的自适应光学荧光终身检眼镜 (AOFLIO)

• 批准号: 10296770
• 负责人: Jennifer J Hunter
• 金额: $ 43.98万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10296770
• 关键词: Acceleration; Adult; Age; Atrophic; Biochemical; Biological Markers; Blindness; Cells; Cellular Structures; Characteristics; Clinical; Clinical Trials; Complex; Computer software; Custom; Cytoplasmic Granules; Data; Development; Diagnosis; Disease; Disease Progression; Electronics; Environment; Evaluation; Eye; Eye diseases; Feedback; Fluorescence; Foundations; Future; Health; Human; Image; Individual; Investigation; Lateral; Learning; Life; Light; Lipofuscin; Measurement; Measures; Melanins; Methodology; Molecular; Monitor; Mosaicism; Mutation; Nature; Ophthalmoscopes; Ophthalmoscopy; Patients; Performance; Phase; Phenotype; Photons; Photoreceptors; Research; Resolution; Retina; Retinal Degeneration; Retinal Diseases; Retinal Dystrophy; Retinal Photoreceptors; Sampling; Scanning; Source; Sparrows; Stargardt' s disease; Structure; Structure of retinal pigment epithelium; System; Variant; Waste Products; adaptive optics; age group; comparative; data acquisition; design; environmental change; experimental study; fluorescence imaging; fluorescence lifetime imaging; fluorophore; healthy aging; high resolution imaging; human subject; imaging modality; improved; in vivo; in vivo imaging; inherited retinal degeneration; innovation; instrumentation; macula; new technology; non-invasive imaging; normal aging; novel therapeutics; prospective; prototype; temporal measurement; tool

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.

项目摘要 视网膜色素上皮（RPE）对维持视网膜的健康和正常功能至关重要。 视网膜是光感受器的一部分，因此与许多导致失明的视网膜疾病有关。在整个 在人的一生中，RPE细胞积累废物，这些废物聚集成荧光脂褐素颗粒。在斯塔加特 疾病时，存在脂褐素积累的加速和分子组成的变化 脂褐质颗粒的脂褐素的荧光使我们能够观察到 视网膜色素上皮细胞与自适应光学扫描光检眼镜。然而，表征RPE细胞 仅从结构和强度不能提供关于细胞健康的足够信息。 从RPE发射的荧光中的时间延迟的测量与荧光的性质有关。 荧光团及其环境，包括脂褐素的组成。适应性发展 人类RPE镶嵌的光学荧光寿命检眼镜（AOFLIO）将提供一个 表征健康和患病眼睛中RPE细胞的重要工具， 功能性生物标志物可用于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病相关的黄斑。荧光寿命将是 通过比较20岁至30岁的成年人受试者中的AOFLIO在视网膜上测量， 70年了识别Stargardt患者RPE层荧光寿命变化的能力 将通过纵向AOFLIO评估疾病（10-30岁）和3年内的进展 在萎缩区域、过渡区和临床正常视网膜中的测量。一些 这些受试者也将使用用于宽视场荧光寿命成像的临床原型进行成像 检眼镜检查（FLIO），生成独一无二的比较数据。此外，目前AOFLIO 仪器将被创新的新技术所取代，以提高光效率 并能分辨出比现在更精细的特征该项目旨在评估 AOFLIO，为我们未来的调查做好准备，将AOFLIO作为一项重要措施， 视网膜退行性疾病的生物标志物，将AOFLIO确立为用于 通过提供关于潜在新疗法效果的快速反馈，帮助临床试验。