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Retinal Vascular Physiology Biomarkers in a 5XFAD Mouse Model of Alzheimer’s Disease

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder that affects the brain and retina and lacks reliable biomarkers for early diagnosis. As amyloid beta (Aβ) manifestations emerge prior to clinical symptoms and plaques of amyloid may cause vascular damage, identification of retinal...

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Autores principales: Matei, Nathanael, Leahy, Sophie, Blair, Norman P., Burford, James, Rahimi, Mansour, Shahidi, Mahnaz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368483/
https://www.ncbi.nlm.nih.gov/pubmed/35954257
http://dx.doi.org/10.3390/cells11152413
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author Matei, Nathanael
Leahy, Sophie
Blair, Norman P.
Burford, James
Rahimi, Mansour
Shahidi, Mahnaz
author_facet Matei, Nathanael
Leahy, Sophie
Blair, Norman P.
Burford, James
Rahimi, Mansour
Shahidi, Mahnaz
author_sort Matei, Nathanael
collection PubMed
description Background: Alzheimer’s disease (AD) is a neurodegenerative disorder that affects the brain and retina and lacks reliable biomarkers for early diagnosis. As amyloid beta (Aβ) manifestations emerge prior to clinical symptoms and plaques of amyloid may cause vascular damage, identification of retinal vascular biomarkers may improve knowledge of AD pathophysiology and potentially serve as therapeutic targets. The purpose of the current study was to test the hypothesis that retinal hemodynamic and oxygen metrics are altered in 5XFAD mice. Methods: Thirty-two male mice were evaluated at 3 months of age: sixteen 5XFAD transgenic and sixteen wild-type mice. Spectral-domain optical coherence tomography, vascular oxygen tension, and blood flow imaging were performed in one eye of each mouse. After imaging, the imaged and fellow retinal tissues were submitted for histological sectioning and amyloid protein analysis, respectively. Protein analysis was also performed on the brain tissues. Results: Retinal physiological changes in venous diameter and blood velocity, arterial and venous oxygen contents, coupled with anatomical alterations in the thickness of retinal cell layers were detected in 5XFAD mice. Moreover, an increase in Aβ42 levels in both the retina and brain tissues was observed in 5XFAD mice. Significant changes in retinal oxygen delivery, metabolism, or extraction fraction were not detected. Based on compiled data from both groups, arterial oxygen content was inversely related to venous blood velocity and nerve fiber/ganglion cell layer thickness. Conclusions: Concurrent alterations in retinal hemodynamic and oxygen metrics, thickness, and tissue Aβ42 protein levels in 5XFAD mice at 3 months of age corresponded to previously reported findings in human AD. Overall, these results suggest that this mouse model can be utilized for studying pathophysiology of AD and evaluating potential therapies.
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spelling pubmed-93684832022-08-12 Retinal Vascular Physiology Biomarkers in a 5XFAD Mouse Model of Alzheimer’s Disease Matei, Nathanael Leahy, Sophie Blair, Norman P. Burford, James Rahimi, Mansour Shahidi, Mahnaz Cells Article Background: Alzheimer’s disease (AD) is a neurodegenerative disorder that affects the brain and retina and lacks reliable biomarkers for early diagnosis. As amyloid beta (Aβ) manifestations emerge prior to clinical symptoms and plaques of amyloid may cause vascular damage, identification of retinal vascular biomarkers may improve knowledge of AD pathophysiology and potentially serve as therapeutic targets. The purpose of the current study was to test the hypothesis that retinal hemodynamic and oxygen metrics are altered in 5XFAD mice. Methods: Thirty-two male mice were evaluated at 3 months of age: sixteen 5XFAD transgenic and sixteen wild-type mice. Spectral-domain optical coherence tomography, vascular oxygen tension, and blood flow imaging were performed in one eye of each mouse. After imaging, the imaged and fellow retinal tissues were submitted for histological sectioning and amyloid protein analysis, respectively. Protein analysis was also performed on the brain tissues. Results: Retinal physiological changes in venous diameter and blood velocity, arterial and venous oxygen contents, coupled with anatomical alterations in the thickness of retinal cell layers were detected in 5XFAD mice. Moreover, an increase in Aβ42 levels in both the retina and brain tissues was observed in 5XFAD mice. Significant changes in retinal oxygen delivery, metabolism, or extraction fraction were not detected. Based on compiled data from both groups, arterial oxygen content was inversely related to venous blood velocity and nerve fiber/ganglion cell layer thickness. Conclusions: Concurrent alterations in retinal hemodynamic and oxygen metrics, thickness, and tissue Aβ42 protein levels in 5XFAD mice at 3 months of age corresponded to previously reported findings in human AD. Overall, these results suggest that this mouse model can be utilized for studying pathophysiology of AD and evaluating potential therapies. MDPI 2022-08-04 /pmc/articles/PMC9368483/ /pubmed/35954257 http://dx.doi.org/10.3390/cells11152413 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Matei, Nathanael
Leahy, Sophie
Blair, Norman P.
Burford, James
Rahimi, Mansour
Shahidi, Mahnaz
Retinal Vascular Physiology Biomarkers in a 5XFAD Mouse Model of Alzheimer’s Disease
title Retinal Vascular Physiology Biomarkers in a 5XFAD Mouse Model of Alzheimer’s Disease
title_full Retinal Vascular Physiology Biomarkers in a 5XFAD Mouse Model of Alzheimer’s Disease
title_fullStr Retinal Vascular Physiology Biomarkers in a 5XFAD Mouse Model of Alzheimer’s Disease
title_full_unstemmed Retinal Vascular Physiology Biomarkers in a 5XFAD Mouse Model of Alzheimer’s Disease
title_short Retinal Vascular Physiology Biomarkers in a 5XFAD Mouse Model of Alzheimer’s Disease
title_sort retinal vascular physiology biomarkers in a 5xfad mouse model of alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368483/
https://www.ncbi.nlm.nih.gov/pubmed/35954257
http://dx.doi.org/10.3390/cells11152413
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