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Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides

Abstract

Photoreceptor cells are incessantly bombarded with photons of light, which, along with the cells' high rate of oxygen metabolism, continuously exposes them to elevated levels of toxic reactive oxygen intermediates (ROIs). Vacancy-engineered mixed-valence-state cerium oxide nanoparticles (nanoceria particles) scavenge ROIs. Our data show that nanoceria particles prevent increases in the intracellular concentrations of ROIs in primary cell cultures of rat retina and, in vivo, prevent loss of vision due to light-induced degeneration of photoreceptor cells. These data indicate that the nanoceria particles may be effective in inhibiting the progression of ROI-induced cell death, which is thought to be involved in macular degeneration, retinitis pigmentosa and other blinding diseases, as well as the ROI-induced death of other cell types in diabetes, Alzheimer's disease, atherosclerosis, stroke and so on. The use of nanoceria particles as a direct therapy for multiple diseases represents a novel strategy and suggests that they may represent a unique platform technology.

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Figure 1: Inhibition of ROIs by nanoceria particles.
Figure 2: Intravitreal injection of nanoceria particles protects rat retina photoreceptor cells from light-induced degeneration.
Figure 3: Nanoceria particles provide pan-retinal protection against light damage.
Figure 4: Nanoceria particles prevent the appearance of TUNEL-positive photoreceptor cells, which occurs days after exposure to damaging light.
Figure 5: Retinal function is protected by the nanoceria particles in a dose-dependent manner.
Figure 6: Nanoceria particles protect photoreceptor cells even when administered after LE.

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Acknowledgements

The authors thank M. Wu and M. Ramsey for technical assistance, J. Ash for advice on construction of data images and M. Dittmar for help with the care and use of the animals. This work was supported by National Institutes of Health grant EY13050, an NEI core grant EY12190, P20 RR017703 from the COBRE program of the National Center for Research Resources, general funds from Presbyterian Health Foundation, and by an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology, Dean McGee Eye Institute. S.S. was supported by the National Science Foundation (NSF BES: 0510270).

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J.C. and J.F.M. conceived and designed the experiments, J.C. performed the experiments, J.F.M. and J.C. analysed the data, S.P. and S.S. generated the nanoceria particles, and J.C., S.P., S.S. and J.F.M. cowrote the paper.

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Correspondence to James F. McGinnis.

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The authors declare no competing financial interests.

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Chen, J., Patil, S., Seal, S. et al. Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides. Nature Nanotech 1, 142–150 (2006). https://doi.org/10.1038/nnano.2006.91

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