Graphene and its derivatives are widely used for a variety of industrial, biomedical, and environmental applications. However, the potential harm caused by exposure of the eyes to graphene-based nanomaterials is scarce. Given the potential for these materials to be used in multiple applications, there is a pressing need to evaluate their ocular toxicity, and understand the relationships between their physico-chemical properties and the resulting toxicity. In this study, the toxicity of PEGylated graphene oxide (PEG-GO) with differing oxidation levels and/or surface charges (positive, negative and neutral charge) was evaluated using two in-vitro models of the eye: primary human corneal epithelial cells and human retinal capillary endothelial cells. The results showed that oxidation level, but not surface charge, had a pivotal effect on the toxicity of graphene-based nanomaterials. Typically, PEG-GO sample with a higher oxidation level caused more serious cytotoxicity than those with a lower oxidation level. Furthermore, by analysis of global gene expression profiles, we found that the foremost cellular response to PEG-GO sample with a high oxidation level was the oxidative stress response. Next, via exploring the underlying molecular mechanism of oxidative stress-induced cytotoxicity, we showed that PEG-GO sample with a high degree of oxidation induced reactive oxygen species (ROS) via NDUFB9-mediated biological pathway. This work has significant implications for design of safe graphene-based nanomaterials for biomedical applications.

中文翻译：

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使用基因表达谱研究氧化态诱导的聚乙二醇化氧化石墨烯在眼组织中的毒性

石墨烯及其衍生物广泛用于各种工业，生物医学和环境应用。然而，由于眼睛暴露于石墨烯基纳米材料而引起的潜在危害很少。鉴于这些材料有可能在多种应用中使用，迫切需要评估其眼毒性，并了解其理化性质与所产生的毒性之间的关系。在这项研究中，使用两种体外方法评估了具有不同氧化水平和/或表面电荷（正电荷，负电荷和中性电荷）的聚乙二醇氧化石墨烯（PEG-GO）的毒性。眼睛模型：原代人角膜上皮细胞和人视网膜毛细血管内皮细胞。结果表明，氧化水平而非表面电荷对石墨烯基纳米材料的毒性具有关键作用。通常，具有较高氧化水平的PEG-GO样品比具有较低氧化水平的PEG-GO样品引起更严重的细胞毒性。此外，通过对全局基因表达谱的分析，我们发现具有高氧化水平的对PEG-GO样品的最重要的细胞反应是氧化应激反应。接下来，通过探索氧化应激诱导的细胞毒性的潜在分子机制，我们表明具有高氧化程度的PEG-GO样品通过NDUFB9介导的生物途径诱导了活性氧（ROS）。