Cerium Oxide Nanoparticles Reduce Microglial Activation and Neurodegenerative Events in Light Damaged Retina.
Cerium Oxide Nanoparticles Reduce Microglial Activation and Neurodegenerative Events in Light Damaged Retina.
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DOI：
10.1371/journal.pone.0140387
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Maccarone R
中科院分区：
文献类型：
--
作者：
Fiorani L;Passacantando M;Santucci S;Di Marco S;Bisti S;Maccarone R
任何视网膜神经变性治疗的首要目标是减缓疾病的进展并维持视觉功能。氧化铈或氧化铈纳米颗粒可以减少氧化应激，而氧化应激在神经退行性变中起着关键作用。我们的目的是研究纳米氧化铈是否能够减轻暴露在高强度光下的神经变性，包括小胶质细胞的激活和相关的炎症过程。将纳米CeO_2玻璃体腔或静脉注射于SD大鼠玻璃体内或静脉内，3周后暴露于1000Lux的光损伤中24小时，在光损伤后1周记录视网膜电图。通过测量外核层厚度和TUNEL染色定量光感受器死亡来评估视网膜变性的进展。免疫组织化学方法检测视网膜应激、神经炎性细胞因子和小胶质细胞活化情况。光损伤后3周，在光感受器外节水平仅检测到玻璃体内注射的纳米CeO_2，视网膜电记录显示纳米CeO_2维持了视觉反应。此外，这种治疗减少了神经元死亡和“热点”延伸，保留了外核层的形态。值得注意的是，在这项工作中，我们首次证明了纳米CeO_2能够减少小胶质细胞的激活和向外核层的迁移。所有这些证据都支持纳米CeO_2在视网膜神经退行性变过程中作为一种有效的治疗剂。
The first target of any therapy for retinal neurodegeneration is to slow down the progression of the disease and to maintain visual function. Cerium oxide or ceria nanoparticles reduce oxidative stress, which is known to play a pivotal role in neurodegeneration. Our aim was to investigate whether cerium oxide nanoparticles were able to mitigate neurodegeneration including microglial activation and related inflammatory processes induced by exposure to high intensity light. Cerium oxide nanoparticles were injected intravitreally or intraveinously in albino Sprague-Dawley rats three weeks before exposing them to light damage of 1000 lux for 24 h. Electroretinographic recordings were performed a week after light damage. The progression of retinal degeneration was evaluated by measuring outer nuclear layer thickness and TUNEL staining to quantify photoreceptors death. Immunohistochemical analysis was used to evaluate retinal stress, neuroinflammatory cytokines and microglial activation. Only intravitreally injected ceria nanoparticles were detected at the level of photoreceptor outer segments 3 weeks after the light damage and electoretinographic recordings showed that ceria nanoparticles maintained visual response. Moreover, this treatment reduced neuronal death and “hot spot” extension preserving the outer nuclear layer morphology. It is noteworthy that in this work we demonstrated, for the first time, the ability of ceria nanoparticles to reduce microglial activation and their migration toward outer nuclear layer. All these evidences support ceria nanoparticles as a powerful therapeutic agent in retinal neurodegenerative processes.