Abstract
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.
Highlights
Nanomaterials which include nano-sized and nano-structured objects, have gained importance in biomedical research and medicine in recent years
This is the first in vivo study to show that nanoceria are rapidly and preferentially taken up and retained in the retina after a single intravitreal injection
The lack of toxic effects in the retina is consistent with our previous findings demonstrating that weekly systemic administration of nanoceria in mice did not have cytotoxic effects in the heart, kidney, brain, lungs, spleen, and liver for a 5-week period [31]
Summary
Nanomaterials which include nano-sized and nano-structured objects, have gained importance in biomedical research and medicine in recent years. Because of the dramatic increase in surface area when synthesized in the nanometer range, nanomaterials exhibit enhanced or unique reactivity that is not found in their macroscopic counterparts. Others are tested for diagnostic, imaging, tissue healing, and surgical aids [1]. Another unique class of nanomaterials, namely the redox-active radical scavenging nanoparticles including fullerenes and cerium oxide nanoparticles (nanoceria or CeNPs), is being developed as bona fide antioxidants for treatment of neurodegenerative diseases [2,3,4]. The enhanced redox capacity of nanoceria is most likely due to the dramatically increased surface to volume ratio of these nanoparticles
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