Retinal vascular dysfunction in the Mthfr 677C>T mouse model of cerebrovascular disease
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Introduction
Investigating retinal biomarkers for Alzheimer’s disease (AD) and related dementias (RD), has increased significantly. We examine retinal vascular health in a mouse containing the ADRD risk variant Mthfr 677C>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 Mthfr 677C>T .
Results
Mice show reduced retinal vascular density and reduced perfusion rate in aging mice, mirroring previously published brain data. Mthfr is widely expressed and colocalizes with vascular cell markers. Proteomics identified common molecular signatures across 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.
