Intrinsic Signal Optoretinography of Retinal Neurovascular Defects in Neurodegeneration

About This Grant

Alzheimer’s disease (AD) is the most common form of dementia, causing memory loss and other serious problems that worsen over time. Detecting AD early is important, but most current tests identify the disease only after significant damage has occurred in the brain. This project focuses on the retina, the light-sensitive tissue at the back of the eye, which is part of the central nervous system and shares many features with the brain. Because the retina can be viewed easily with imaging tools, it may provide an early window into brain health. The research team is developing a new imaging technique called intrinsic signal optoretinography. This method measures how different parts of the retina respond to light using fast, noninvasive imaging technology. By studying changes in the retina, the researchers aim to detect signs of the disease before structural damage is visible. These early changes could help scientists and doctors monitor disease progression and evaluate treatments, without the need for invasive procedures. The project also supports eye and brain research and will provide training opportunities for students in science and engineering. This project aims to establish intrinsic signal optoretinography as a noninvasive, quantitative method for detecting early functional biomarkers of AD in the retina. The research will use a custom-built, multi-modal optical coherence tomography (OCT) system that integrates polarization-sensitive imaging, parfocal light stimulation, and flexible spatiotemporal acquisition to capture intrinsic optical signals across multiple retinal layers. Three major neurovascular biomarkers will be studied in 3xTg-AD transgenic and wild-type mouse models: (1) photoreceptor hyperexcitability, (2) delayed and spatially spreading intrinsic optical signals responses in the inner plexiform layer, and (3) impaired flicker-induced vasodilation, measured using Doppler OCT. These functional biomarkers will be correlated with structural changes identified by OCT and OCT angiography, such as retinal thinning and microvascular degeneration. The imaging system is designed to support longitudinal studies across both preclinical and symptomatic stages of AD. Expected outcomes include new tools for early disease detection, preclinical drug screening, and longitudinal monitoring in AD models. Broader impacts include the development of a versatile functional imaging platform, interdisciplinary training of undergraduate and graduate students, and STEM outreach through hands-on biomedical optics education. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.