Extracellular vesicle-mediated long-range communication in stressed retinal pigment epithelial cell monolayers

Biochim Biophys Acta Mol Basis Dis. 2018 Aug;1864(8):2610-2622. doi: 10.1016/j.bbadis.2018.04.016. Epub 2018 Apr 21.


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.

Keywords: Age-related macular degeneration; Exosomes; Extracellular vesicles; HDAC6; Retinal pigment epithelium; Tight junctions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Communication*
  • Cell Line
  • Extracellular Vesicles / metabolism*
  • Extracellular Vesicles / pathology
  • Histone Deacetylase 6 / metabolism*
  • Humans
  • Macular Degeneration / metabolism*
  • Macular Degeneration / pathology
  • Oxidative Stress*
  • Retinal Pigment Epithelium / metabolism*
  • Retinal Pigment Epithelium / pathology
  • Swine


  • HDAC6 protein, human
  • Histone Deacetylase 6