Abstract
Purpose: :
Looking at ocular changes in Alzheimer’s disease (AD), studies have shown the major hallmarks of AD, e.g. amyloid plaques formation, neurofibrillary tangles and neuronal loss in retinae of transgenic mouse models of AD. Here, we investigated the role of structural and functional changes that blood vessels undergo in AD.
Methods: :
5- to 12-month-old double transgenic mice over-expressing human APPswe and mutant presenilin 1 with exon 9 deletion (APPswe/PS1-dE9) were raised and compared to backround genotype mice. Retinal vascularisation was determined by fundus fluorescence angiography. Electroretinograms (ERG), autofluorescence imaging and histopathologic examinations were assessed.
Results: :
Although immunoreactivity for Isolecitin revealed a regular endothelium and vascular branching, fluorescence angiograms demonstrated reduced peripheral retinal perfusion in 12-month-old transgenic mice. Electroretinography presented mild scotopic and photopic alterations. In addition, Amyloid ß protein (Aß) positive immuno-staining was present in inner retinal vessels. Starting at 5 months of age, transgenic mice showed paravascular glial cell degeneration.
Conclusions: :
Taken together, we are the first to our knowledge to demonstrate reduced retinal blood perfusion in a murine model of AD with altered neuro-retinal signal transduction. Para-vascular astrocyte degeneration is the earliest pathological finding we observed indicating that retinal vascular pathology is an early symptom in AD. The easy accessibility of the retinal vascular tissue could therefore make it an efficient tool to monitor AD progression.
Keywords: retinal degenerations: cell biology • blood supply • microglia