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

Navjot Shah, Masakii Ishii, Carlene Brandon, Zsolt Ablonczy, Jingwen Cai, Yutao Liu, C. James Chou, Bärbel Rohrer

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2610-2622
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number8
StatePublished - Aug 2018


  • Age-related macular degeneration
  • Exosomes
  • Extracellular vesicles
  • HDAC6
  • Retinal pigment epithelium
  • Tight junctions

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology


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