Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1864, Issue 8, Pages 2610-2622Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2018.04.016
Keywords
Retinal pigment epithelium; Extracellular vesicles; Exosomes; Tight junctions; HDAC6; Age-related macular degeneration
Funding
- National Institutes of Health (NIH) [R01EY019320]
- Department of Veterans Affairs [RX000444, BX003050]
- South Carolina SmartState Endowment [MUCR 2236010 8B571 9923 88]
- BrightFocus Foundation [G2016023]
- Glaucoma Foundation
- Glaucoma Research Foundation
- Startup Fund from the Medical College of Georgia
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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.
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