Intracellular amyloid beta alters the tight junction of retinal pigment epithelium in 5XFAD mice.
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.
Fight against Angiogenesis-Related Blindness Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea; Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea.
Sung Wook
SW
Park
Fight against Angiogenesis-Related Blindness Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
Jin Hyoung
JH
Kim
Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea.
Inhee
I
Mook-Jung
SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
Kyu-Won
KW
Kim
Department of Life Sciences, Life Sciences Concentration GIST (Gwangju Institute of Science and Technology), Gwangju, Korea.
Woo Jin
WJ
Park
Department of Ophthalmology, College of Medicine, Seoul National University, Seoul, Korea; Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea. Electronic address: jiani4@snu.ac.kr.
Kyu Hyung
KH
Park
Fight against Angiogenesis-Related Blindness Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea; Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea; Department of Ophthalmology, College of Medicine, Seoul National University, Seoul, Korea. Electronic address: steph25@snu.ac.kr.
Jeong Hun
JH
Kim
D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001813:Blood-Retinal Barrier / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D008268:Macular Degeneration / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008822:Mice, Transgenic; D062793:Occludin / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
D016229:Amyloid beta-Peptides; D062793:Occludin; D010446:Peptide Fragments; D062826:Zonula Occludens-1 Protein; C075222:amyloid beta-protein (1-42)
Age-related macular degeneration; Aging; Alzheimer's disease; Aβ; Outer blood retinal barrier; Retina; Retinal pigment epithelium; Tight junction; Transgenic mice