Yttrium oxide nanoparticles prevent photoreceptor death in a light-damage model of retinal degeneration.

Yttrium oxide nanoparticles prevent photoreceptor death in a light-damage model of retinal degeneration.
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DOI:
10.1016/j.freeradbiomed.2014.07.013
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发表时间:
2014-10
影响因子:
7.4
通讯作者:
Naash, Muna I.
Naash, Muna I.
中科院分区:
医学1区
文献类型:
--
作者:
Mitra, Rajendra N.;Merwin, Miles J.;Han, Zongchao;Conley, Shannon M.;Al-Ubaidi, Muayyad R.;Naash, Muna I.

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光感受器(PR)细胞容易积累活性氧(ROS)和氧化应激。ROS的产生和细胞抗氧化防御之间的不平衡导致许多不同眼病状态下的PR变性和失明。氧化钇(Y2O3)纳米颗粒(NPs)由于其非化学计量的晶体缺陷而成为优异的自由基清除剂。在这里,我们利用小鼠光应激模型来测试Y2O3 NPs(直径~ 10-14 nm)改善视网膜氧化应激相关变性的功效。我们的研究表明,在急性光应激前两周,玻璃体内注射这些NPs,剂量范围为0.1 μM至5.0 μM,可以保护pr免于退化。这种保护反映在结构上(即减少与光相关的外核层变薄)和功能上,即保存暗位和光位视网膜电图振幅。我们还观察到急性光胁迫后立即给予NPs对细胞结构和功能的保存,尽管保存的幅度较小,并且只有1.0 μM至5.0 μM的剂量有效。我们发现Y2O3 NPs在玻璃体内传递后无毒且耐受性良好。我们的研究结果表明,Y2O3 NPs具有惊人的抗氧化作用,并且随着进一步的探索,可能是治疗多种形式视网膜变性相关氧化应激的绝佳策略。
Photoreceptor (PR) cells are prone to accumulation of reactive oxygen species (ROS) and oxidative stress. An imbalance between the production of ROS and cellular antioxidant defenses contributes to PR degeneration and blindness in many different ocular disease states. Yttrium oxide (Y2O3) nanoparticles (NPs) are excellent free radical scavengers due to their non-stoichiometric crystal defects. Here we utilize a murine light stress model to test the efficacy of Y2O3 NPs (~ 10–14 nm in diameter) in ameliorating retinal oxidative stress-associated degeneration. Our studies demonstrate that intravitreal injections of these NPs at doses ranging from 0.1 μM to 5.0 μM two weeks prior to acute light stress protects PRs from degeneration. This protection is reflected both structurally (i.e. decreased light-associated thinning of the outer nuclear layer) and functionally, i.e. in preservation of scotopic and photopic electroretinogram amplitudes. We also observe preservation of structure and function when NPs are delivered immediately after acute light stress, although the magnitude of the preservation is smaller, and only doses ranging from 1.0 μM to 5.0 μM were effective. We show that the Y2O3 NPs are non-toxic and well-tolerated after intravitreal delivery. Our results suggest that Y2O3 NPs have astonishing antioxidant benefits, and with further exploration, may be an excellent strategy for the treatment of oxidative stress associated with multiple forms of retinal degeneration.
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