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.

Cerium oxide nanoparticles protect against Aβ-induced mitochondrial fragmentation and neuronal cell death

“…Nanoceria decreased oxidative stress in rat retinal neurons in vitro and single intravitreal injections prevented light-induced oxidative damage in albino rats in vivo. 49 In addition, nanoceria protected against H 2 O 2 -induced cell death in retinal ganglion cells and ROS-induced blindness in vivo. 49 Nanoceria injections into the vitreous of the eye of very low-density lipoprotein receptor knockout mice, a mouse model of macular degeneration, reduced oxidative stress, tyrosine nitration and VEGF-mediated neovascularization linked to blindness.…”

“…49 In addition, nanoceria protected against H 2 O 2 -induced cell death in retinal ganglion cells and ROS-induced blindness in vivo. 49 Nanoceria injections into the vitreous of the eye of very low-density lipoprotein receptor knockout mice, a mouse model of macular degeneration, reduced oxidative stress, tyrosine nitration and VEGF-mediated neovascularization linked to blindness. 50 Finally, nanoceria might also be cardioprotective as intravenous injection of nanoceria attenuated left ventricle dysfunction and dilation of the heart of monocyte chemo-attractant protein 1 transgenic mice.…”

Valence State Manipulation of Cerium Oxide Nanoparticles on a Titanium Surface for Modulating Cell Fate and Bone Formation

“…In particular, their capability to quench free radicals (i.e., antioxidant activity) give CeONPs great potential for use in therapy of diseases caused by reactive oxygen species (ROS), such as retinal degeneration,16 cardiovascular pathology,17 neurodegenerative disorders,18 and spinal cord injury 19. Most of the CeONP characteristics are endowed by the co‐existence of both Ce 4+ and Ce 3+ oxidation states.…”

“…This mixed valence state of CeONPs has therapeutic potential due to the possibility of scavenging ROS in cells 16, 23. Previous in vitro studies have shown that CeONPs can react catalytically with superoxide and hydrogen peroxide to mimic the biological actions of superoxide dismutase (SOD)[[qv: 23b,24]] and catalase 25.…”

Adsorption of Nanoceria by Phosphocholine Liposomes

“…2,4 For example, it was reported that nanoceria can scavenge reactive oxygen species (ROS) in living systems with superoxide dismutase and catalase-like activities. 2,[7][8][9] In a few cases, nanoceria protected cells from oxidative stress induced by ROS or radiation. [10][11][12][13][14] It was also reported that nanoceria protects normal cells but not cancer cells.…”