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J. L. Goldberg, M. N. De Silva, A. D. Weisman, A. Shirodkar, P. Handa, Y. Hu; Retinal Ganglion Cell Regeneration: A Nanoparticle Strategy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4803. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Stimulating regenerative growth of retinal ganglion cells (RGCs) remains a major goal of ophthalmology because RGCs fail to regenerate their axons after injury or in degenerative diseases such as glaucoma, optic neuritis, optic ischemia and other optic neuropathies. Interestingly, nanotechnology is an emerging field where nano-structured materials are being researched in many biomedical applications including medical diagnostics, imaging, and therapeutics. We are exploring novel nanotechnology-based approaches by which nanoparticles could be used to augment RGC axon regeneration.
We have investigated how magnetic and non-magnetic nanoparticles ranging in size from 50nm to 400nm interact with optic nerve glia and RGCs in vitro and in vivo. We asked whether these nanoparticles can be incorporated into axons and cells. Nanoparticle incorporation into retinal ganglion cells was measured after 4, 8, 12, and 24hrs as assayed via light and electron microscopy.
In vivo, nanoparticles were localized to the site of injection with no acute particle-specific toxicity observed. In the optic nerve injections, a subset of the nanoparticles were transported along RGC axons to their cell bodies. In vitro, we found quantitatively similar magnetic nanoparticle endocytosis by embryonic and postnatal RGCs. Electron micrographs suggested that nanoparticles are contained in membrane-bound vesicles, and the distribution of vesicle size ranged between 200-1200nm, and were independent of the age of neuron, cell type, and in vitro culture period. Furthermore, 65-75 percent of the nanoparticles were membrane bound; the remainder were found to be internalized.
Nanoparticles can be membrane bound or endocytosed by RGCs in vitro and in vivo, without particle specific toxicity. We envision that functionalizing nanoparticles for optimized binding to neurons will enable us better understand nanoparticle-RGC interactions. Such understanding will be useful in developing nanotechnology-based diagnostics and therapeutics for the diseases in the eye. Our ultimate goal is to stimulate axon regeneration for the repair of the retina after injury.
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