Nanoceria extend photoreceptor cell lifespan in tubby mice by modulation of apoptosis/survival signaling pathways.
Nanoceria extend photoreceptor cell lifespan in tubby mice by modulation of apoptosis/survival signaling pathways.
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DOI：
10.1016/j.nbd.2011.03.004
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发表时间：
2011-06
影响因子：
6.1
通讯作者：
McGinnis, James F.
中科院分区：
文献类型：
--
作者：
Kong, Li;Cai, Xue;Zhou, Xiaohong;Wong, Lily L.;Karakoti, Ajay S.;Seal, Sudipta;McGinnis, James F.
氧化铈纳米粒子是一种无机抗氧化剂，具有模拟神经保护酶超氧化物歧化酶和过氧化氢酶的催化活性。我们之前在大鼠光损伤模型中表明，纳米眼珠可以保持视网膜形态并防止视网膜功能丧失。本研究以表现出遗传性早期进行性耳蜗和视网膜变性的纯合子管状突变小鼠为模型，测试纳米粒延缓视网膜变性进展的能力。在出生后第10天以及随后的P20和P30天，Tubby小鼠全身、心内注射20µl 1mM的生理盐水，而注射生理盐水和未注射生理盐水的野生型（或杂合的Tubby）分别作为注射对照组和未注射对照组。对P34小鼠进行视网膜功能、形态学和信号通路基因表达测定。我们的数据表明，纳米粒通过减少活性氧（ROS），上调神经保护相关基因的表达来保护视网膜；下调凋亡信号通路和/或上调存活信号通路以减缓光感受器退化。这些数据表明，纳米粒在遗传性视网膜变性和大多数眼部疾病的治疗中具有巨大的潜力。
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.
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