July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Retinal vascular reactivity in a mouse model of Alzheimer’s disease.
Author Affiliations & Notes
  • Jeremiah K.H. Lim
    Optometry and Vision Science, The University of Melbourne, Melbourne, Victoria, Australia
  • Qiao-xin Li
    Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia
  • Holly Rose Chinnery
    Optometry and Vision Science, The University of Melbourne, Melbourne, Victoria, Australia
  • Zheng He
    Optometry and Vision Science, The University of Melbourne, Melbourne, Victoria, Australia
  • Algis J Vingrys
    Optometry and Vision Science, The University of Melbourne, Melbourne, Victoria, Australia
  • Bang V Bui
    Optometry and Vision Science, The University of Melbourne, Melbourne, Victoria, Australia
  • Christine Tram Oanh Nguyen
    Optometry and Vision Science, The University of Melbourne, Melbourne, Victoria, Australia
  • Footnotes
    Commercial Relationships   Jeremiah Lim, None; Qiao-xin Li, None; Holly Chinnery, None; Zheng He, None; Algis Vingrys, None; Bang Bui, None; Christine Nguyen, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3946. doi:
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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)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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]).

Conclusions : 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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