Early detection of Alzheimer's disease (AD) is crucial for prompt interventions to preserve brain function. Neuronal hyperexcitability promises a biomarker of early-stage AD. However, in vivo, detection of neuronal hyperexcitability is technically challenging. With a custom-designed optical coherence tomography (OCT), this study demonstrated the feasibility of using retinal intrinsic optical signal (IOS) imaging, also known as optoretinography (ORG), for detecting photoreceptor hyperexcitability associated with early-stage AD. Morphological OCT analysis revealed detectable thinning of retinal thickness in 3xTg-AD mice from 5 months of age. In contrast, functional ORG disclosed increased photoreceptor hyperexcitability of 3xTg-AD mice from 4 months of age.
Delayed dark adaptation due to homeostatic imbalances in the retina is a subclinical symptom of retinal neurodegenerative diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP), the leading cause of irreversible vision loss. Thus, objective measurement of dark adaptation can facilitate the early diagnosis of various retinal diseases. However, there is a lack of noninvasive methods capable of simultaneous assessment of both anatomical arrangement and functional interactions among retinal cells. Here we demonstrate intrinsic signal optoretinography (ORG) of dark adaptation in the C57BL/6J mouse retina. Optical coherence tomography (OCT) imaging for ORG was continuously performed during dark adaptation at every 5 min interval for 30 minutes, and the spatiotemporal relationship of retinal activities was examined. We observed three imaging features in the retina under different light conditions. First, it was notable that dark adaptation caused a reduction in outer retinal thickness. Second, in the light-adapted retina, the 3rd band of the outer retina was distinguished, which was absent in the dark-adapted retina, and a hypo-reflective band between the 3rd and 4th band was only observed in the light-adapted retina. Third, OCT intensity of the 2nd outer retinal band markedly decreased in the dark-adapted retina. A strong positive correlation between morphophysiological activities was also confirmed. OCT-based ORG enables the measurement of dynamic progress of dark adaptation in a quantitative way with layer-specificity, which can aid in diagnosing early-stage retinal diseases.
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