TNFα-mediated priming of mesenchymal stem cells enhances their neuroprotective effect on retinal ganglion cells

Ben Mead, Xitiz Chalming, Donald Zack, Zubair Ahmed, Stanislav Tomarev

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)
124 Downloads (Pure)


Purpose: To determine whether priming of bone marrow mesenchymal stem cells (MSCs) by signals from injured retina, particularly tumor necrosis factor α (TNFα), increase their exosomes’ neuroprotective efficacy on retinal ganglion cells (RGCs).

Methods: MSCs were primed with retinal cell culture conditioned medium, with or without the TNFα blocker etanercept or TNFα prior to isolation of exosomes. MSC conditioned medium or exosomes were added to rat retinal cultures or human stem cell–derived retinal ganglion cell (hRGC) cultures, and RGC neuroprotective effects were quantified. Luminex assays were used to compare primed versus unprimed exosomes.

Results: MSC conditioned medium and exosomes exerted a significant neuroprotective effect on injured rat and hRGC. This effect was significantly increased after MSCs were primed with retinal conditioned medium or TNFα. Blocking of TNFα signaling with etanercept prevented priming-induced RGC neuroprotective efficacy. Priming increased PEDF and VEGF-AA exosomal abundance.

Conclusions: MSC exosomes promote RGC survival not just in rodent retinal cultures but also with hRGC. Their efficacy can be further enhanced through TNFα priming with the mechanism of action potentially mediated, at least in part, through increased levels of PEDF and VEGF-AA.
Original languageEnglish
Article number6
Number of pages10
JournalInvestigative Ophthalmology & Visual Science (IOVS)
Issue number2
Publication statusPublished - 7 Feb 2020


  • exosomes
  • extracellular vesicles
  • TNFα
  • mesenchymal stem cells
  • glaucoma
  • priming
  • retinal ganglion cell

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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