Intracellular amyloid beta alters the tight junction of retinal pigment epithelium in 5XFAD mice

Extracellular deposit of amyloid beta (A beta) is a common pathologic feature in both age-related macular degeneration (AMD) and Alzheimer's disease, but the role of intracellular A beta on the tight junction of the retinal pigment epithelium (RPE) is unknown. In this study, we investigated the intracellular A beta expression and its role on the outer blood retinal barrier in the retina of 5XFAD mice, a mouse model of Alzheimer's disease. The retina of 5XFAD mice showed the pathologic features of AMD with intracellular A beta in the RPE. As intracellular A beta accumulated, zonular occludens-1 and occludin were markedly attenuated and lost their integrity as tight junctions in the RPE of 5XFAD mice. Also, A beta(42) uptake by ARPE-19 cells induced the tight junction breakdown of zonular occludens-1 and occludin without cell death. These results implicate that intracellular A beta(42) could play a role in the breakdown of the outer blood retinal barrier in 5XFAD mice. Thus, we suggested that 5XFAD mice could be a mouse model of dry AMD with regard to the A beta(42) related pathology. (C) 2014 Elsevier Inc. All rights reserved.