July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Retinal thinning of inner layers is associated with visual cortex atrophy in a mouse model of Alzheimer’s disease: a longitudinal in vivo multimodal study
Author Affiliations & Notes
  • Antonio F Ambrosio
    Coimbra Institute for Clinical and Biomedical Research (iCBR), University Coimbra, Coimbra, Portugal
    CNC.IBILI Consortium, University Coimbra, Coimbra, Portugal
  • Samuel Chiquita
    Coimbra Institute for Clinical and Biomedical Research (iCBR), University Coimbra, Coimbra, Portugal
    CNC.IBILI Consortium, University Coimbra, Coimbra, Portugal
  • João Castelhano
    CNC.IBILI Consortium, University Coimbra, Coimbra, Portugal
    Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University Coimbra, Coimbra, Portugal
  • Mário Ribeiro
    CNC.IBILI Consortium, University Coimbra, Coimbra, Portugal
    Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University Coimbra, Coimbra, Portugal
  • José Sereno
    CNC.IBILI Consortium, University Coimbra, Coimbra, Portugal
    Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University Coimbra, Coimbra, Portugal
  • Elisa J Campos
    Coimbra Institute for Clinical and Biomedical Research (iCBR), University Coimbra, Coimbra, Portugal
    CNC.IBILI Consortium, University Coimbra, Coimbra, Portugal
  • Paula I Moreira
    CNC.IBILI Consortium, University Coimbra, Coimbra, Portugal
    Center for Neuroscience and Cell Biology (CNC), University Coimbra, Coimbra, Portugal
  • Miguel Castelo-Branco
    CNC.IBILI Consortium, University Coimbra, Coimbra, Portugal
    Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University Coimbra, Coimbra, Portugal
  • Footnotes
    Commercial Relationships   Antonio Ambrosio, None; Samuel Chiquita, None; João Castelhano, None; Mário Ribeiro, None; José Sereno, None; Elisa Campos, None; Paula Moreira, None; Miguel Castelo-Branco, None
  • Footnotes
    Support  Santa Casa Mantero Belard Award 2015 (MB-1049-2015), FCT (SFRH/BD/52045/2012, SFRH/BPD/93672/2013, PEst UID/NEU/04539/2013 and MEDPERSYST SAICTPAC/0010/2015), COMPETE-FEDER (POCI-01-0145-FEDER-007440 and POCI-01-0145-FEDER-016428) and Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000008: BrainHealth 2020 and CENTRO-01-0145-FEDER-000016:BIGDATIMAGE).
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4787. doi:
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    • Get Citation

      Antonio F Ambrosio, Samuel Chiquita, João Castelhano, Mário Ribeiro, José Sereno, Elisa J Campos, Paula I Moreira, Miguel Castelo-Branco; Retinal thinning of inner layers is associated with visual cortex atrophy in a mouse model of Alzheimer’s disease: a longitudinal in vivo multimodal study. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4787.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : It has been claimed that the retina can be used as a window to study brain disorders. In Alzheimer’s disease (AD), it still remains controversial whether brain and retinal changes are associated, and there is a clear need to clarify if the retina can indeed mirror changes in the brain. We aimed to understand when changes start appearing in the retina and brain, how changes progress and if they are correlated, to fill in the gaps related with the missing links between retina and brain pathology in AD.

Methods : We carried out a longitudinal study using a triple transgenic mouse model of AD (3xTg-AD) and age matched wild type (WT) animals (males). Several parameters were evaluated in vivo, in the same animals, at 4, 8, 12 and 16 months of age, in the retina and brain. Retinal structure was evaluated by OCT (line and circle scans) and retinal physiology was evaluated by ERG and PERG. Brain visual cortex structure was evaluated by magnetic resonance imaging (MRI).

Results : The thickness of total retina, and the thickness of GCL+IPL, significantly decreased in 3xTg-AD mice, comparing to WT mice, at all time points. At 16 months, the total retinal thickness decreased from 196.3 µm in WT to 176.1 µm in 3xTg-AD mice (p<0.001), and the thickness of GGL+IPL decreased from 69.5 µm in WT to 53.5 µm in 3xTg-AD mice (p<0.001) (circle scan). However, the ONL thickness in 3xTg-AD mice was significantly higher at 12 and 16 months (p<0.001). The ERGs showed that 3xTg-AD mice had a significantly higher scotopic b-wave amplitude at all time points. The a-wave amplitude was not significantly different from the WT. In the photopic flicker, the first harmonic amplitude in 3xTg-AD mice was higher than in WT (p<0.001), at all time points. PERG recordings did not show statistically significant differences between 3xTg-AD and WT mice. The visual cortex grey matter volume in 3xTg-AD mice was reduced at all time points (F(1,8)=104.95; p<0.0002). A Spearman correlation test showed a positive correlation between retinal thickness and grey matter volume and a negative correlation between ERG amplitude and gray matter volume in the visual cortex.

Conclusions : These results show that the retina is a mirror of the brain. The notion that the retina can be a mirror of AD progression supports the possibility of using the eye as an additional tool for the early AD diagnosis.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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