Wednesday, December 4, 2024
12/4/2024
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.
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