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催化纳米氧化铈优先保留在大鼠视网膜中,并且在玻璃体内注射后没有细胞毒性。

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

机构信息

Department of Ophthalmology, University of Oklahoma Health Sciences Center, College of Medicine, and Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States of America.

出版信息

PLoS One. 2013;8(3):e58431. doi: 10.1371/journal.pone.0058431. Epub 2013 Mar 11.

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.

摘要

氧化铈纳米颗粒(纳米氧化铈)具有催化和再生自由基清除活性。纳米氧化铈维持细胞氧化还原平衡的能力使它们成为治疗视网膜疾病的理想候选物,这些疾病的发展与氧化损伤密切相关。我们已经证明,我们稳定的水分散纳米氧化铈可延缓啮齿动物模型中感光细胞的变性,并可预防 vldlr 突变小鼠的病理性视网膜新生血管形成。本研究的目的是确定单次玻璃体内注射后纳米氧化铈的时空分布,并确定纳米氧化铈是否对健康大鼠视网膜有任何毒性作用。使用电感耦合等离子体质谱法(ICP-MS),我们发现纳米氧化铈被视网膜迅速吸收,即使在 120 天后,这种组织也优先保留纳米氧化铈。即使在这种长期暴露后,我们也没有观察到纳米氧化铈对视网膜功能或细胞结构有任何急性或长期的负面影响。由于纳米氧化铈在低剂量下有效、无毒且在视网膜中保留时间长,我们得出结论,纳米氧化铈是治疗已知涉及氧化应激发病机制的视网膜疾病的有前途的眼科治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6443/3594235/e62e3c3cc99e/pone.0058431.g001.jpg

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