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Shuhong Jiang, Karen Chang, Kin-Sang Cho, Anton Lennikov, Wai Lydia Tai, Ajay Ashok, Dongfeng Chen; Visual and retinal function changes in a mouse model of Alzheimer Disease. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4119 – F0356.
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© ARVO (1962-2015); The Authors (2016-present)
It is emerging that there are early changes of visual function in association with Alzheimer’s disease (AD). In this work, we propose to test the potential changes and when the changes start to appear in the retinas o AD mice, using the triple transgenic mouse model (3×Tg-AD).
We carried out a longitudinal study in AD (3×Tg-AD) mice at 2, 4, 6, 12 months of ages. Age and sex-matched wild-type mice were used as controls. Visual acuity and contrast sensitivity were assessed by optomotor response (OMR). Retina functional changes were evaluated by electroretinography (ERG) to record the ganglion cell dominated positive scotopic threshold response (pSTR) that were elicited with the dimmest flashes (0.0001765 cd/m2). Outer retinal layer functions were recorded by ERG maximum scotopic response (Xenon lamp, 2cd. cd/m2), light-adapted photopic (Xenon light, 600 cd/m2), S cone test (green light, 13 cd.s/m2), and M cone test (blue light, 13 cd.s/m2).
Significantly reduced visual contrast sensitivity (CS) was detected in 3xTG-AD mice at as early as 2 months (2M) of age compared to age-matched wild-type control mice. Notably, female AD mice showed better CS than male mice when examined at 2M of age. Starting from 6M old, there was significant reduction of visual acuity (VA) in 3xTG-AD mice comparing with age-matched WT control mice. The ERG pSTR amplitude in 3xTg-AD mice was also significantly reduced at 4M of age comparing to WT, and this difference persisted throughout the later ages examined (4M, 99.308+/-7.194 vs 107.307+/-6.986, p < 0.01; 12M, 56.39+/-15.56 vs 78.77+/-16.89, p < 0.05 by two-way ANOVA). 3xTg-AD mice also revealed a significantly higher scotopic b-wave amplitude and light-adapted photopic response than WT mice starting from 6M of age. The a-wave amplitude and S cone test or M cone test in AD mice were not significantly different from the WT at all time points.
Our results suggest visual function deficit at a very early-stage of AD. Sex differences in the spatial frequency threshold should be considered. The pattern of neuronal dysfunction in AD mice occurs primarily in the inner retina and probably progresses to encompass the outer retina with age.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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