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

Mead, Ben ORCID: https://orcid.org/0000-0001-5855-0097, Chamling, Xitiz, Zack, Donald J., Ahmed, Zubair and Tomarev, Stanislav 2020. TNFα-mediated priming of mesenchymal stem cells enhances their neuroprotective effect on retinal ganglion cells. Investigative Ophthalmology & Visual Science 61 , 6. 10.1167/iovs.61.2.6

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Optometry and Vision Sciences
Additional Information:	This work is licensed under a Creative Commons Attribution 4.0 International License
Publisher:	Association for Research in Vision and Ophthalmology (ARVO)
ISSN:	0146-0404
Date of First Compliant Deposit:	16 January 2020
Date of Acceptance:	14 November 2019
Last Modified:	04 May 2023 05:40
URI:	https://orca.cardiff.ac.uk/id/eprint/128692

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