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Jeremiah K.H. Lim, Qiao-xin Li, Holly Rose Chinnery, Zheng He, Algis J Vingrys, Bang V Bui, Christine Tram Oanh Nguyen; Retinal vascular reactivity in a mouse model of Alzheimer’s disease.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3946.
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© ARVO (1962-2015); The Authors (2016-present)
Previous reports showed that retinal vessel diameters are narrower and less reactive in Alzheimer’s disease (AD) patients, compared with controls. Here, we consider if a systemic stressor (gas perturbation) may identify abnormalities in vasoreactivity across a range of ages in a mouse model of AD.
Familial AD mouse model B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax (5xFAD) was studied at three ages (n = 5xFAD/WT, 6-month-old [mo]: 9/13, 12mo: 12/13, 17mo: 10/14). Retinal vessels within one disc diameter of the optic nerve were imaged (428 ± 5 nm) at 10 sec intervals over 12 min. Each animal underwent both hyperoxic (100% O2) or hypercapnic (10% CO2) breathing with the order assigned in a randomised fashion. The first 2 min were taken as baseline, followed by 5 min of gas breathing; then 5 mins recovery. An additional 5 min was allowed for recovery before switching gases. Retinal images were analysed in FIJI using the Vessel Diameter plugin. Change in vessel diameter was expressed relative to baseline and modelled using a sigmoidal function to determine maximal change (%) and speed of change. A non-parametric bootstrap was used to determine the confidence limits around each parameter.
Retinal arteries were thinner in 6 mo 5xFAD (90.3% ± 2.4, p<0.05) relative to controls, but veins were not different (p=0.13). There was no difference in baseline vessel diameter (arteries and veins) in 12 mo 5xFAD mice (p=0.1, 0.9). At 17 months, 5xFAD mice showed narrower veins (89.0% + 3.3, p<0.05) compared with control but no difference in arteries (p=0.9). During hyperoxia, 6 mo 5xFAD veins (-9.5% [-7.5 – -11.6] vs WT -12.7% [-10.0 – -15.6], p< 0.05), 12mo 5xFAD arteries (-8.2% [-7.3 – -11.4] vs WT -11.8% [-10.4 – -14.9], p< 0.05) and veins (-7.4% [-6.5 – -9.2] vs WT -13.0% [-11.9 – -15.1], p< 0.05) showed reduced vasoconstriction. Hypercapnia induced vasodilation was impaired in 5xFAD mice at 12mo (art: 7.1% [6.5 – 8.5] vs WT 9.1% [7.1 – 10.9], veins: 8.3% [6.9 – 9.4] vs WT 10.9% [9.6 – 14.7]).
Basal retinal artery diameter was narrower at the early stages of the disease. At the oldest age, retinal veins were narrower. At 6 and 12 months of age, gas perturbation revealed that vascular reactivity was impaired in 5xFAD mice. Assessing vessel diameter and controlled gas breathing probes of vascular reactivity might be useful for the purpose of detecting AD-related retinal changes.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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