Neuroprotective Effects of Human Mesenchymal Stem Cells and Platelet-Derived Growth Factor on Human Retinal Ganglion Cells

Author:

Osborne Andrew1ORCID,Sanderson Julie2,Martin Keith R.1345

Affiliation:

1. John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom

2. School of Pharmacy, University of East Anglia, Norwich, United Kingdom

3. Cambridge NIHR Biomedical Research Centre, Cambridge, United Kingdom

4. Eye Department, Addenbrooke's Hospital, Cambridge, United Kingdom

5. Wellcome Trust-Medical Research Council, Stem Cell Institute, Cambridge, United Kingdom

Abstract

Abstract Optic neuropathies such as glaucoma occur when retinal ganglion cells (RGCs) in the eye are injured. Strong evidence suggests mesenchymal stem cells (MSCs) could be a potential therapy to protect RGCs; however, little is known regarding their effect on the human retina. We, therefore, investigated if human MSCs (hMSCs), or platelet-derived growth factor (PDGF) as produced by hMSC, could delay RGC death in a human retinal explant model of optic nerve injury. Our results showed hMSCs and the secreted growth factor PDGF-AB could substantially reduce human RGC loss and apoptosis following axotomy. The neuroprotective pathways AKT, ERK, and STAT3 were activated in the retina shortly after treatments with labeling seen in the RGC layer. A dose dependent protective effect of PDGF-AB was observed in human retinal explants but protection was not as substantial as that achieved by culturing hMSCs on the retina surface which resulted in RGC cell counts similar to those immediately post dissection. These results demonstrate that hMSCs and PDGF have strong neuroprotective action on human RGCs and may offer a translatable, therapeutic strategy to reduce degenerative visual loss.

Funder

International Glaucoma Association

Cambridge Eye Trust

Jukes Glaucoma Research Fund

Humane Research Trust

Wellcome Trust

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

Reference52 articles.

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