Campus Units

Genetics, Development and Cell Biology, Biomedical Sciences, Veterinary Clinical Sciences, Neuroscience

Document Type


Publication Version

Accepted Manuscript

Publication Date


Journal or Book Title

Experimental Eye Research





First Page


Last Page





The pupose of this study was to determine the viability of cell-based delivery of brain-derived neurotrophic factor (BDNF) from genetically modified mesenchymal stem cells (MSCs) for neuroprotection of RGC-5 cells. RGC-5 cells were differentiated with the protein kinase inhibitor staurosporine (SS) and exposed to the cellular stressors glutamate or H2O2. As a neuroprotective strategy, these cells were then co-cultured across a membrane insert with mesenchymal stem cells (MSCs) engineered with a lentiviral vector for production of BDNF (BDNF-MSCs). As a positive control, recombinant human BDNF (rhBDNF) was added to stressed RGC-5 cells. After SS differentiation RGC-5s developed neuronal-like morphologies, and a significant increase in the proportion of RGC-5s immunoreactive for TuJ-1 and Brn3a was observed. Differentiated RGC-5s also had prominent TrkB staining, demonstrating expression of the high-affinity BDNF receptor. Treatment of SS differentiated RGC-5s with glutamate or H2O2, produced significant cell death (56.0 ± 7.02 and 48.90 ± 4.58% of control cells, respectively) compared to carrier-solution treated cells. BDNF-delivery from MSCs preserved more RGC-5 cells after treatment with glutamate (80.0 ± 5.40% cells remaining) than control GFP expressing MSCs (GFP-MSCs, 57.29 ± 1.89%, p < 0.01). BDNF-MSCs also protected more RGC-5s after treatment with H2O2 (65.6 ± 3.47%) than GFPMSCs (46.0 ± 4.20%, p < 0.01). We have shown survival of differentiated RGC-5s is reduced by the cellular stressors glutamate and H2O2. Additionally, our results demonstrate that genetically modified BDNF-producing MSCs can enhance survival of stressed RGC-5 cells and therefore, may be effective vehicles to deliver BDNF to retinal ganglion cells affected by disease.


This is a manuscript from Experimental Eye Research 89 (2009): 538, doi: 10.1016/j.exer.2009.05.013. Posted with permission.

Copyright Owner

Elsevier Ltd



File Format