Retinal Aging in 3× Tg-AD Mice Model of Alzheimer's Disease

Guimarães, Pedro; Serranho, Pedro; Martins, João; Moreira, Paula I.; Ambrósio, António Francisco; Castelo‐Branco, Miguel; Bernardes, Rui

doi:10.3389/fnagi.2022.832195

Cited by 7 publications

(16 citation statements)

References 28 publications

(36 reference statements)

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“…Based on OCT imaging, retinal changes induced by neurodegenerative diseases have been found, including changes in retinal layer thickness (Cunha et al, 2016 ; Song et al, 2020 ; Salobrar-García et al, 2021 ). Recently, we have also shown that retinal texture biomarkers can help discriminate between age-matched healthy controls and animal models of Alzheimer's disease (AD) in the early stages (Nunes et al, 2019 ; Ferreira et al, 2020 , 2022 ; Guimarães et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Normative mice retinal thickness: 16-month longitudinal characterization of wild-type mice and changes in a model of Alzheimer's disease

Batista

Guimarães

Martins

et al. 2023

Front. Aging Neurosci.

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Animal models of disease are paramount to understand retinal development, the pathophysiology of eye diseases, and to study neurodegeneration using optical coherence tomography (OCT) data. In this study, we present a comprehensive normative database of retinal thickness in C57BL6/129S mice using spectral-domain OCT data. The database covers a longitudinal period of 16 months, from 1 to 16 months of age, and provides valuable insights into retinal development and changes over time. Our findings reveal that total retinal thickness decreases with age, while the thickness of individual retinal layers and layer aggregates changes in different ways. For example, the outer plexiform layer (OPL), photoreceptor inner segments (ILS), and retinal pigment epithelium (RPE) thickened over time, whereas other retinal layers and layer aggregates became thinner. Additionally, we compare the retinal thickness of wild-type (WT) mice with an animal model of Alzheimer's disease (3 × Tg-AD) and show that the transgenic mice exhibit a decrease in total retinal thickness compared to age-matched WT mice, with statistically significant differences observed at all evaluated ages. This normative database of retinal thickness in mice will serve as a reference for future studies on retinal changes in neurodegenerative and eye diseases and will further our understanding of the pathophysiology of these conditions.

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Section: Introductionmentioning

confidence: 99%

Normative mice retinal thickness: 16-month longitudinal characterization of wild-type mice and changes in a model of Alzheimer's disease

Batista

Guimarães

Martins

et al. 2023

Front. Aging Neurosci.

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“…The expression of both transgenes is controlled by the mouse Thy1.2 promoter [ 33 , 40 , 43 ]. A total of six different studies have utilised OCT to analyse the retina in this model: Chiquita et al [ 44 ] conducted a longitudinal analysis, examining male mice at 4, 8, 12, and 16 months of age and comparing them with age-matched WT mice ( C57BL/6J ); Song et al [ 45 ] employed female 3xTg-AD mice and B6129SF2/J mice as WT group; Gardner et al [ 46 ] performed a cross-sectional study with 20 3xTg-AD mice (16 males and 4 females) at different ages (2, 4, 7 and 10 months), comparing them with 12 C57BL/6J mice (only males) as the control group; Ferreira et al [ 47 ] utilised the 3xTg-AD model to compare the effects of disease and aging with a normative database of the C57BL6/129S model, using male mice at various ages (1, 2, 3, and 4 months); Guimarães et al [ 48 ] analysed 60 male 3xTg-AD mice and 57 male C57BL6/129S mice at different ages (1, 2, 3, 4, 8, 12, and 16 months) in a longitudinal study; Batista et al [ 49 ] examined both eyes of 144 male mice, including 57 3xTg-AD mice and 57 WT mice, at various ages (1, 2, 3, 4, 8, 12, and 16 months). …”

Section: Resultsmentioning

confidence: 99%

“…Guimarães et al [ 48 ] analysed 60 male 3xTg-AD mice and 57 male C57BL6/129S mice at different ages (1, 2, 3, 4, 8, 12, and 16 months) in a longitudinal study;…”

Section: Resultsmentioning

confidence: 99%

“…Both eyes were examined using OCT in: (i) the APP/PS1 model in the studies conducted by Harper et al (2020) [ 42 ] and Georgevsky et al (2019) [ 41 ]; (ii) the 3xTg-AD model in the works of Ferreira et al, Guimarães et al, Chiquita et al, and Batista et al model [ 44 , 47 , 48 , 49 ]; and (iii) the TgCRND8 model analysed by Buccarello et al [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

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OCT Imaging in Murine Models of Alzheimer’s Disease in a Systematic Review: Findings, Methodology and Future Perspectives

Sánchez-Puebla,

López-Cuenca,

Salobrar-García

et al. 2024

Biomedicines

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The murine models of Alzheimer’s disease (AD) have advanced our understanding of the pathophysiology. In vivo studies of the retina using optical coherence tomography (OCT) have complemented histological methods; however, the lack of standardisation in OCT methodologies for murine models of AD has led to significant variations in the results of different studies. A literature search in PubMed and Scopus has been performed to review the different methods used in these models using OCT and to analyse the methodological characteristics of each study. In addition, some recommendations are offered to overcome the challenges of using OCT in murine models. The results reveal a lack of consensus on OCT device use, retinal area analysed, segmentation techniques, and analysis software. Although some studies use the same OCT device, variations in other parameters make the direct comparison of results difficult. Standardisation of retinal analysis criteria in murine models of AD using OCT is crucial to ensure consistent and comparable results. This implies the application of uniform measurement and segmentation protocols. Despite the absence of standardisation, OCT has proven valuable in advancing our understanding of the pathophysiology of AD.

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“…Bernardes et al reported that the mice harboring three human mutant genes of AD showed a thicker RNFL + GCL until 4 months old ( 48 ). Aβ deposits may contribute to the inflammatory processes, neuronal degeneration, and aging in the retina and finally change retinal thickness ( 60 , 61 ).…”

Section: Discussionmentioning

confidence: 99%

Retinal thickness changes in different subfields reflect the volume change of cerebral white matter hyperintensity

Teng²,

Jia³

et al. 2022

Front. Neurol.

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PurposeTo investigate the relationship between the retinal thickness in different subfields and the volume of white matter hyperintensity (WMH), with the hope to provide new evidence for the potential association between the retina and the brain.MethodsA total of 185 participants aged over 40 years were included in our study. Magnetic resonance imaging (MRI) was used to image the WMH, and WMH volume was quantitatively measured by a specific toolbox. The thickness of the total retina, the retinal nerve fiber layer (RNFL), and the ganglion cell and inner plexiform layer (GCIP) was measured by optical coherence tomography (OCT) in nine subfields. The association between retinal thickness and WMH volume was demonstrated using binary logistic regression and Pearson correlation analysis.ResultsParticipants were divided into two groups by the WMH volume (‰, standardized WMH volume) median. In the quartile-stratified binary logistic regression analysis, we found that the risk of higher WMH volume showed a positive linear trend correlation with the thickness of total retina (95% CI: 0.848 to 7.034; P for trend = 0.044)/ GCIP (95% CI: 1.263 to 10.549; P for trend = 0.038) at the central fovea, and a negative linear trend correlation with the thickness of nasal inner RNFL (95% CI: 0.086 to 0.787; P for trend = 0.012), nasal outer RNFL (95% CI: 0.058 to 0.561; P for trend = 0.004), and inferior outer RNFL (95% CI: 0.081 to 0.667; P for trend = 0.004), after adjusting for possible confounders. Correlation analysis results showed that WMH volume had a significant negative correlation with superior outer RNFL thickness (r = −0.171, P = 0.02) and nasal outer RNFL thickness (r = −0.208, P = 0.004).ConclusionIt is suggested that central fovea and outer retina thickness are respectively associated with WMH volume. OCT may be a biological marker for early detection and longitudinal monitoring of WMH.

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Retinal Aging in 3× Tg-AD Mice Model of Alzheimer's Disease

Cited by 7 publications

References 28 publications

Normative mice retinal thickness: 16-month longitudinal characterization of wild-type mice and changes in a model of Alzheimer's disease

Normative mice retinal thickness: 16-month longitudinal characterization of wild-type mice and changes in a model of Alzheimer's disease

OCT Imaging in Murine Models of Alzheimer’s Disease in a Systematic Review: Findings, Methodology and Future Perspectives

Retinal thickness changes in different subfields reflect the volume change of cerebral white matter hyperintensity

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