Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK73104, USA.
Neurobiol Dis. 2011 Jun;42(3):514-23. doi: 10.1016/j.nbd.2011.03.004. Epub 2011 Mar 30.
Cerium oxide nanoparticles, nanoceria, are inorganic antioxidants that have catalytic activities which mimic those of the neuroprotective enzymes superoxide dismutase and catalase. We have previously shown that nanoceria preserve retinal morphology and prevent loss of retinal function in a rat light damage model. In this study, the homozygous tubby mutant mouse, which exhibits inherited early progressive cochlear and retinal degeneration, was used as a model to test the ability of nanoceria to slow the progression of retinal degeneration. Tubby mice were injected systemically, intracardially, with 20 μl of 1mM nanoceria in saline, at postnatal day 10 and subsequently at P20 and P30 whereas saline injected and uninjected wild type (or heterozygous tubby) served as injected and uninjected controls, respectively. Assays for retinal function, morphology and signaling pathway gene expression were performed on P34 mice. Our data demonstrate that nanoceria protect the retina by decreasing Reactive Oxygen Species (ROS), up-regulating the expression of neuroprotection-associated genes; down-regulating apoptosis signaling pathways and/or up-regulating survival signaling pathways to slow photoreceptor degeneration. These data suggest that nanoceria have significant potential as global agents for therapeutic treatment of inherited retinal degeneration and most types of ocular diseases.
氧化铈纳米颗粒，纳米氧化铈，是一种无机抗氧化剂，具有模拟超氧化物歧化酶和过氧化氢酶等神经保护酶的催化活性。我们之前的研究表明，纳米氧化铈可保持视网膜形态并防止光损伤模型大鼠的视网膜功能丧失。在这项研究中，我们使用纯合突变形（tubby）突变小鼠作为模型，该模型表现出遗传性进行性耳蜗和视网膜变性，以测试纳米氧化铈减缓视网膜变性进展的能力。在出生后第 10 天和第 20 天及第 30 天，通过系统注射（intracardially）20 μl 1mM 的纳米氧化铈盐水溶液的方式，向突变形小鼠体内注射，而生理盐水注射和未注射的野生型（或杂合突变形）小鼠分别作为注射和未注射对照。在 P34 只小鼠上进行视网膜功能、形态和信号通路基因表达的检测。我们的数据表明，纳米氧化铈通过减少活性氧（ROS）来保护视网膜，上调与神经保护相关的基因表达；下调细胞凋亡信号通路和/或上调存活信号通路，以减缓光感受器变性。这些数据表明，纳米氧化铈具有作为治疗遗传性视网膜变性和大多数类型眼病的全身性治疗药物的巨大潜力。
