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M. N. De Silva, J. L. Goldberg; Magnetic Nanoparticle-Based Technology for Repairing Optic Nerve. Invest. Ophthalmol. Vis. Sci. 2007;48(13):234.
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Retinal Ganglion Cells (RGCs) fail to regenerate their axons after injury and in degenerative diseases such as glaucoma, optic neuritis, optic ischemia and other optic neuropathies. In animal models, blocking glial-associated inhibitory signals and providing exogenous positive neurotrophic signals can slightly enhance axon regeneration and functional recovery, although typically only a few axons regenerate and at a very slow rate. Furthermore, little is known about the trophic signaling of axon regeneration of CNS neurons. Interestingly, over 20 years ago it was demonstrated that tension plays a key role in stimulating the growth of neurites in vitro and in vivo. Here we ask whether novel nanotechnology-based approaches could be used to manipulate axons to overcome inhibitory substrates and to enhance the trophic signaling of axon growth.
Here we investigated how commercially available magnetic nanoparticles ranging in size from 50 to 400nm interact with RGC axons in vitro and in vivo in the optic nerve. Specifically, we asked whether nanoparticles can be incorporated into axons and cells in vitro and in vivo. After 24hrs, the presence and localization of nanoparticles in the microinjected tissue and cultured cells were examined via light and electron microscopy.
We found excellent localization of the nanoparticles at the site of injection, as well as retrograde transport of the nanoparticles back to the neuronal cell bodies. When we immunostained for neuronal and glial markers, we found little to no toxicity of the injected nanoparticles. Also, we found that nanoparticles can be taken up by cells or attched on cell surface in vitro. Finally, we examined neurons and glia in vivo and found no toxic effects of the magnetic nanoparticles, with or without applied magnetic fields.
Thus magnetic nanoparticles can bind to and be endocytosed by RGCs in vitro and in vivo, without apparent toxicity. Ongoing experiments are directed at identifying the subcellular localization of the nanoparticles, functionalizing magnetic nanoparticles for optimized binding to axons, and using magnetic fields to exert forces on neuronal growth cones in vitro and in vivo. Our ultimate goal is to stimulate axon regeneration for the repair of the optic nerve after injury.
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