Retinal vascular dysfunction in the Mthfr677C>T mouse model of cerebrovascular disease

Abstract

IntroductionInvestigating retinal biomarkers for Alzheimers disease (AD) and related dementias (RD), has increased significantly. We examine retinal vascular health in a mouse containing the ADRD risk variant Mthfr677C>Tto determine if changes in retina mirror similar changes in cerebrovasculature. MethodsMorphology 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. ResultsMice 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. DiscussionResults 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.