TY - JOUR
T1 - Extracellular vesicle-mediated long-range communication in stressed retinal pigment epithelial cell monolayers
AU - Shah, Navjot
AU - Ishii, Masakii
AU - Brandon, Carlene
AU - Ablonczy, Zsolt
AU - Cai, Jingwen
AU - Liu, Yutao
AU - Chou, C. James
AU - Rohrer, Bärbel
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/8
Y1 - 2018/8
N2 - Retinal pigment epithelium (RPE) alterations in age-related macular degeneration occur in patches, potentially involving long-distance communication between damaged and healthy areas. Communication along the epithelium might be mediated by extracellular vesicles (EVs). To test this hypothesis, EVs were collected from supernatants of polarized ARPE-19 and primary porcine RPE monolayers for functional and biochemical assays. EVs from oxidatively stressed donor cells reduced barrier function in recipient RPE monolayers when compared to control EVs. The effect on barrier function was dependent on EV uptake, which occurred rapidly with EVs from oxidatively stressed donor cells. Mass spectrometry-based proteomic analysis of EVs identified HDAC6, which is known to reduce tight junction stability. Activity assays confirmed the presence of HDAC6 in EVs, and EV transfer assays using HDAC6 inhibitors confirmed its effect in monolayers. These findings demonstrate that EVs can communicate stress messages to healthy RPE cells, potentially contributing to RPE dysfunction.
AB - Retinal pigment epithelium (RPE) alterations in age-related macular degeneration occur in patches, potentially involving long-distance communication between damaged and healthy areas. Communication along the epithelium might be mediated by extracellular vesicles (EVs). To test this hypothesis, EVs were collected from supernatants of polarized ARPE-19 and primary porcine RPE monolayers for functional and biochemical assays. EVs from oxidatively stressed donor cells reduced barrier function in recipient RPE monolayers when compared to control EVs. The effect on barrier function was dependent on EV uptake, which occurred rapidly with EVs from oxidatively stressed donor cells. Mass spectrometry-based proteomic analysis of EVs identified HDAC6, which is known to reduce tight junction stability. Activity assays confirmed the presence of HDAC6 in EVs, and EV transfer assays using HDAC6 inhibitors confirmed its effect in monolayers. These findings demonstrate that EVs can communicate stress messages to healthy RPE cells, potentially contributing to RPE dysfunction.
KW - Age-related macular degeneration
KW - Exosomes
KW - Extracellular vesicles
KW - HDAC6
KW - Retinal pigment epithelium
KW - Tight junctions
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U2 - 10.1016/j.bbadis.2018.04.016
DO - 10.1016/j.bbadis.2018.04.016
M3 - Article
C2 - 29684588
AN - SCOPUS:85046728726
SN - 0925-4439
VL - 1864
SP - 2610
EP - 2622
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 8
ER -