Catalytic nanoceria are preferentially retained in the rat retina and are not cytotoxic after intravitreal injection

• Published in: PloS one Vol. 8; no. 3; p. e58431
• Main Authors: Wong, Lily L, Hirst, Suzanne M, Pye, Quentin N, Reilly, Christopher M, Seal, Sudipta, McGinnis, James F
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.03.2013; Public Library of Science (PLoS)
• Subjects: Animal models; Animals; Biology; Biomedical materials; Catalysis; Cell culture; Cerium; Cerium - administration & dosage; Cerium - chemistry; Cerium - pharmacokinetics; Cerium - toxicity; Cerium oxides; Chemistry; Cytotoxicity; Degeneration; Diabetic retinopathy; Drug dosages; Electroretinography; Free Radical Scavengers - administration & dosage; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacokinetics; Free Radical Scavengers - toxicity; Health sciences; Inductively coupled plasma; Inductively coupled plasma mass spectrometry; Injection; Intravitreal Injections; Low density lipoprotein receptors; Mass spectrometry; Mass spectroscopy; Medical treatment; Medicine; Nanomaterials; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanoparticles - toxicity; Osteopathic medicine; Oxidation-Reduction - drug effects; Oxidative Stress; Photoreceptors; Rare earth metal compounds; Rats; Retina; Retina - drug effects; Retina - metabolism; Retinal degeneration; Spatial distribution; Tissue Distribution; Toxicity; Vascularization; United States > US; Virginia; Oklahoma
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0058431

Cerium oxide nanoparticles (nanoceria) possess catalytic and regenerative radical scavenging activities. The ability of nanoceria to maintain cellular redox balance makes them ideal candidates for treatment of retinal diseases whose development is tightly associated with oxidative damage. We have demonstrated that our stable water-dispersed nanoceria delay photoreceptor cell degeneration in rodent models and prevent pathological retinal neovascularization in vldlr mutant mice. The objectives of the current study were to determine the temporal and spatial distributions of nanoceria after a single intravitreal injection, and to determine if nanoceria had any toxic effects in healthy rat retinas. Using inductively-coupled plasma mass spectrometry (ICP-MS), we discovered that nanoceria were rapidly taken up by the retina and were preferentially retained in this tissue even after 120 days. We also did not observe any acute or long-term negative effects of nanoceria on retinal function or cytoarchitecture even after this long-term exposure. Because nanoceria are effective at low dosages, nontoxic and are retained in the retina for extended periods, we conclude that nanoceria are promising ophthalmic therapeutics for treating retinal diseases known to involve oxidative stress in their pathogeneses.