Intrinsic signal optoretinography of early photoreceptor abnormality in Alzheimer’s disease mice

Abstract

Purpose : This study is to demonstrate the feasibility of using retinal intrinsic optical signal (IOS) imaging for objective optoretinography of photoreceptor abnormality in Alzheimer’s disease (AD) mice.

Methods : A custom-designed optical coherence tomography (OCT) with a visible light retinal stimulator was employed for retinal IOS imaging. Alzheimer’s disease (3xTg-AD) and age-matched control (C57BL/6J) mice were imaged at 1, 2, 3, 4, 5, and 6 months. The retinal layer thickness and band intensity were quantitatively compared in control and AD mice. For light-evoked IOS imaging, each recording consisted of 100 time-lapse OCT B-scans collected with a 200 Hz frame speed. The IOS recording included 3 phases, a 250 ms pre-stimulation phase, a 10 ms stimulation on phase, and a 240 ms post-stimulation phase. The intensity background was computed by averaging all the frames in the pre-stimulation phase. The IOS of an individual pixel was defined as the intensity change divided by the background intensity. The average IOS in the ellipsoid zone (EZ) and the interdigitation zone (IZ) of each retina was calculated and analyzed by a one-way ANOVA test.

Results : Morphological OCT analysis revealed inner retina thinning in the 3xTg-AD mice, compared to the control group (Fig. 1D2). Significant difference was observed between the control and 3xTg-AD groups from the 5^th month. On the contrary, the out retina thickness did not show a structural difference. However, functional OCT analysis disclosed significant IOS differences in the outer retina, i.e., the photoreceptor layer (Fig. 1E). It was observed that the IOS stays stable in the control mice after 2^nd month; it keeps increasing in the 3xTg-AD mice (Fig. 1F). Significant difference was observed from the 4^th month.

Conclusions : Morphological OCT revealed AD caused structural abnormality in the inner retina. On the contrary, functional OCT-enabled intrinsic signal optoretinography of AD caused physiological abnormality in photoreceptors at the outer retina. By providing both morphological and physiological information, quantitative OCT promises a noninvasive method for early detection and treatment assessment of AD.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.