Intrinsic signal optoretinography revealing AD-induced retinal photoreceptor hyperexcitability before a detectable morphological abnormality

Abstract

Neuronal hyperexcitability promises an early biomarker of Alzheimer’s disease (AD). However, in vivo detection of neuronal hyperexcitability in the brain is technically challenging. The retina, one part of the central nervous system, presents a unique window for noninvasive monitoring of the brain function. This study aims to test the feasibility of using intrinsic signal optoretinography (ORG) for mapping retinal hyperexcitability associated with early-stage AD. Custom-designed optical coherence tomography (OCT) was employed for both morphological measurement and functional ORG of wild-type mice and 3xTg-AD mice. Comparative analysis revealed AD-induced retinal photoreceptor hyperexcitability prior to detectable structural degeneration.