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Updated: Sep 13, 2025
Optimization of the Retinal Vein Occlusion Mouse Model to Limit Variability
Published on: August 6, 2021
Retinal vascular dysfunction in the Mthfr677C>T mouse model of cerebrovascular disease
Alaina M Reagan1, Michael MacLean1, Travis L Cossette1
1The Jackson Laboratory, Bar Harbor, Maine, USA.
Introduction:
Investigations of retinal biomarkers for Alzheimer's disease (AD) and AD and related dementias (ADRD), has increased significantly. We examine retinal vascular health in a mouse containing the ADRD risk variant Mthfr677C>T to determine if changes in retina mirror similar changes in cerebrovasculature.
Methods:
Morphology and function of retinal vasculature and neurons were assessed using in vivo imaging, immunohistochemistry, and pattern electroretinography. RNAscope and proteomics were employed to determine Mthfr gene expression and differential protein expression in mice carrying Mthfr677C>T.
Results:
Mice show age- and sex-dependent retinal vascular deficits, displaying similarities to previously published brain data. Mthfr is widely expressed and co-localizes with vascular cell markers. Proteomics identified common molecular signatures across the brain and retina.
Discussion:
Results demonstrate that Mthfr-dependent vascular phenotypes occur in brain and retina similarly. These data suggest that assessing age and genetic-driven changes within retinal vasculature represents a minimally invasive method to predict AD-related cerebrovascular damage.
Highlights:
Mthfr677C>T retinal vascular phenotypes align with cerebrovascular phenotypes. Mthfr677C>T brain and retina share Alzheimer's disease (AD)-)relevant differentially expressed proteins. Retinal imaging may provide insight regarding genetic risk for vascular dysfunction.
Insights
Investigating the Mthfr677C>T variant in mice, this study found that retinal vascular changes mirror brain changes associated with Alzheimer's disease and related dementias (ADRD). Retinal imaging may offer a non-invasive way to detect genetic risks for cerebrovascular damage.
Area of Science:
- Neuroscience
- Ophthalmology
- Genetics
Background:
- Alzheimer's disease (AD) and related dementias (ADRD) research increasingly focuses on retinal biomarkers.
- The Mthfr677C>T variant is a known risk factor for ADRD.
Purpose of the Study:
- To investigate retinal vascular health in mice with the Mthfr677C>T variant.
- To determine if retinal changes reflect cerebrovascular alterations in ADRD.
Main Methods:
- In vivo imaging, immunohistochemistry, and electroretinography assessed retinal morphology and function.
- RNAscope and proteomics analyzed Mthfr gene and protein expression.
- Comparative analysis of brain and retinal vascular phenotypes.
Main Results:
- Mice with Mthfr677C>T exhibited age- and sex-dependent retinal vascular deficits.
- Retinal findings mirrored previously reported brain vascular changes.
- Proteomics revealed shared molecular signatures between brain and retina.
- Mthfr expression was widespread and co-localized with vascular markers.
Conclusions:
- Mthfr-dependent vascular changes occur similarly in both brain and retina.
- Retinal vasculature changes can serve as a minimally invasive indicator of AD-related cerebrovascular damage.
- Retinal imaging may provide insights into genetic predispositions for vascular dysfunction relevant to ADRD.
