FEB 07, 2011
Mounting evidence suggests that supplemental therapy with neurotrophic factors (NTFs) either by intravitreal injections or by gene therapy is neuroprotective in models of optic nerve injuries, including optic nerve transection (ONT) and glaucoma. In order to take this approach one step further, investigators induced rat and human bone marrow-derived mesenchymal stem cells (MSCs) to secrete high levels of neurotrophic factors in a rat model of optic nerve transaction.
Mean retinal ganglion cell survival at eight days post-transection increased significantly after injection of untreated human NTF-SCs or mesenchymal stem cells (MSCs) compared to injection of saline. In a separate experiment, rat NTF-SCs were not found to be more neuroprotective than saline. Immunohistochemistry demonstrated that human-derived MSC, human NTF-SCs and rat-derived NTF-SCs survived at least 24 days after injection.
The authors conclude that increased secretion of neurotrophic factors by human MSCs and NTF-SCs has significant importance in preventing retinal ganglion cell death and in protecting the injured optic nerve. The fact that both NTF-SCs and MSCs were neuroprotective suggests that even small amounts of different types of neurotrophic factors can be neuroprotective. However, the lack of significant difference between the effects of the two types of cells suggests that in a severe injury like ONT, delivering higher amounts of different neurotrophic factors is insufficient to prevent death.
Taken as a whole, the data from this study suggest that it may be more advantageous to use stem cells as vectors that secrete and deliver neurotrophic factors. At the same time, efforts should be made to find ways to improve the integration of stem cells into the retinal ganglion cell layer, facilitate their differentiation into retinal ganglion cells, and induce axonal sprouting in order to form neuronal connections within the retina and to the brain.