Extracellular deposit of amyloid beta (Aβ) is a common pathologic feature in both age-related macular degeneration (AMD) and Alzheimer's disease, but the role of intracellular Aβ on the tight junction of the retinal pigment epithelium (RPE) is unknown. In this study, we investigated the intracellular Aβ 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 Aβ in the RPE. As intracellular Aβ accumulated, zonular occludens-1 and occludin were markedly attenuated and lost their integrity as tight junctions in the RPE of 5XFAD mice. Also, Aβ₄₂ uptake by ARPE-19 cells induced the tight junction breakdown of zonular occludens-1 and occludin without cell death. These results implicate that intracellular Aβ₄₂ 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 Aβ₄₂ related pathology.