Article | Published:

Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides

Nature Nanotechnology volume 1, pages 142150 (2006) | Download Citation

Subjects

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    , & Neurodegenerative diseases and oxidative stress. Biomed. Pharmacother. 58, 39–46 (2004).

  2. 2.

    et al. Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Diabetes Metab. Res. Rev. 19, 442–455 (2003).

  3. 3.

    , , & Opsin distribution and protein incorporation in photoreceptors after experimental retinal detachment. Exp. Eye Res. 53, 629–640 (1991).

  4. 4.

    , & The retina: oxidative stress and diabetes. Redox. Rep. 8, 187–192 (2003).

  5. 5.

    , , , & The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv. Ophthalmol. 45, 115–134 (2000).

  6. 6.

    , , & Electrical conductivity and lattice defects in nanocrystalline cerium oxide thin films. J. Am. Ceram. Soc. 84, 2007–2014 (2001).

  7. 7.

    Characterization of surface defects on epitaxial CeO2(001) films. Surf. Sci. 437, 207–214 (1999).

  8. 8.

    Computer modeling of surfaces and defects on cerium dioxide. Surf. Sci. 339, 337–352 (1995).

  9. 9.

    Defect equilibria for extended point-defects, with application to nonstoichiometric ceria. J. Phys. Chem. Solids 34, 1839–1845 (1973).

  10. 10.

    , , , & lattice defects and oxygen storage capacity of nanocrystalline ceria and ceria-zirconia. J. Phys. Chem. A 104, 11110–11116 (2000).

  11. 11.

    et al. Size dependency variation in lattice parameter and valency states in nanocrystalline cerium oxide. Appl. Phys. Lett. 87, 1–3 (2005).

  12. 12.

    , , & Lattice relaxation of monosize CeO2-x nanocrystalline particles. Appl. Surf. Sci. 152, 53–56 (1999).

  13. 13.

    & Action spectrum of retinal light-damage in albino rats. Invest. Ophthalmol. Vis. Sci. 24, 285–287 (1983).

  14. 14.

    et al. Protection of Rpe65-deficient mice identifies rhodopsin as a mediator of light-induced retinal degeneration. Nat. Genet. 25, 63–66 (2000).

  15. 15.

    et al. Unique retina cell phenotypes revealed by immunological analysis of recoverin expression in rat retina cells. J. Neurosci. Res. 55, 252–260 (1999).

  16. 16.

    & A parametric study of retinal light damage in pigmented and albino rats, in The Effects of Constant Light on Visual Processes (eds & ) 135–159 (Plenum Press, New York, 1980).

  17. 17.

    , , & Continuing damage to rat retinal DNA during darkness following light exposure. Photochem. Photobiol. 71, 559–566 (2000).

  18. 18.

    , , & Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration. Prog. Retin. Eye Res. 24, 275–306 (2005).

  19. 19.

    , , , & Role of trivalent La and Nd dopants in lattice distortion and oxygen vacancy generation in cerium oxide nanoparticles. Appl. Phys. Lett. 88, 1–3 (2006).

  20. 20.

    , , & Raman scattering and lattice defects in nanocrystalline CeO2 thin films. Solid State Ionics 149, 99–105 (2002).

  21. 21.

    , , & Light-induced apoptosis: differential timing in the retina and pigment epithelium. Exp. Eye Res. 64, 963–970 (1997).

  22. 22.

    & Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic. Biol. Med. 30, 1191–1212 (2001).

  23. 23.

    , , , & Redox ranking of inducers of a cancer-protective enzyme via the energy of their highest occupied molecular orbital. Free Radic. Biol. Med. 36, 1418–1423 (2004).

  24. 24.

    & Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photooxidative damage. Proc. Natl. Acad. Sci. USA 101, 10446–10451 (2004).

  25. 25.

    , , , & Neuroprotective therapies for Alzheimer's disease. Curr. Pharm. Des. 12, 705–717 (2006).

  26. 26.

    & Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mech. Ageing Dev. 122, 945–962 (2001).

  27. 27.

    & Oxidative stress and atherosclerosis. Pathophysiology 13, 129–142 (2006).

  28. 28.

    , & Reperfusion injury. Plast. Reconstr. Surg. 117, 1024–1033 (2006).

  29. 29.

    & Induction of glutamine synthetase in embryonic neural retina: its suppression by the gliatoxic agent alpha-aminoadipic acid. Brain Res. 227, 103–119 (1981).

  30. 30.

    , , & Glial cells dissociated from newborn and aged mouse brain. J. Neurosci. Res. 11, 253–262 (1984).

  31. 31.

    , , & Immunocytochemical localization of glycerol-3-phosphate dehydrogenase in rat oligodendrocytes. Brain Res. 196, 287–305 (1980).

  32. 32.

    , & Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem. Res. Toxicol. 5, 227–231 (1992).

  33. 33.

    et al. In vivo protection of photoreceptors from light damage by pigment epithelium-derived factor. Invest Ophthalmol. Vis. Sci. 42, 1646–1652 (2001).

Download references

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).

Author information

Affiliations

  1. Oklahoma Center for Neuroscience

    • Junping Chen
    •  & James F. McGinnis
  2. Dean A. McGee Eye Institute

    • Junping Chen
    •  & James F. McGinnis
  3. Department of Cell Biology

    • James F. McGinnis
  4. Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA

    • James F. McGinnis
  5. Surface Engineering and Nanotechnology Facility, Advanced Materials Processing Analysis Center, Mechanical Materials Aerospace Engineering, Nanoscience and Technology Center, University of Central Florida, 4000 Central Florida Boulevard, Orlando, Florida 32816, USA

    • Swanand Patil
    •  & Sudipta Seal

Authors

  1. Search for Junping Chen in:

  2. Search for Swanand Patil in:

  3. Search for Sudipta Seal in:

  4. Search for James F. McGinnis in:

Contributions

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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to James F. McGinnis.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nnano.2006.91

Further reading