Characterizing ocular pathology in an animal model of Alzheimer’s disease

Previous studies have characterized common pathological hallmarks of Alzheimer’s disease such as amyloid accumulation and plaque consolidation in the brain. The difficulty in accessing the brain in vivo has remained a barrier to the diagnosis or measuring the progression of the disease. Studies have shown that, in addition to amyloid deposition, angiogenesis and increased blood-brain barrier permeability are present in the brain of Alzheimer’s patients and animal models. Our study investigated whether these pathologies could be recapitulated in a more accessible organ associated with the central nervous system: the eyes. Using the Tg2576 model of Alzheimer’s disease, a transgenic mouse model which expresses human amyloid, an increase in amyloid was seen in the eyes of these mice and it was determined that the amyloid coalesced primarily around retinal blood vessels. This link between amyloid and ocular vasculature prompted a pilot study using a proteome profiler and found increased proangiogenic factors in the eyes and brains of the Tg2576 mouse, 20 proteins of which were upregulated in both organs. Performing further analyses of functional pathways on these findings revealed several reoccurring proteins in several pathways across both organs, including chemokines and fibroblast growth factors. Additional evidence of angiogenic processes was determined via the increased expression of CD105, a marker of neoangiogenesis, in whole eye homogenates of Tg2576 mice. When the distribution of the increased vasculature was examined, while the Tg2576 retina did not have increased amounts of CD105⁺CD31⁺ microvessels, the choroid did have more CD31⁺ vessels. Importantly, expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin was decreased in the Tg2576 retinal pigment epithelia and in whole eye homogenates, respectively. Along with evidence of an increased presence of albumin in whole eye homogenates, these results suggest that there is increased permeability in the Tg2576 eyes. Our findings provide new insights into concurrent pathologies exhibited in a commonly used Alzheimer’s mouse model, suggesting that the eyes may be used as a proxy for brain pathology.Science, Faculty ofMicrobiology and Immunology, Department ofGraduat