Ocular exposure to metal oxide engineered nanomaterials (ENMs) is common as exemplified by zinc oxide (ZnO), a major constituent of sunscreens and cosmetics. The ocular surface that includes the transparent cornea and its protective tear film are common sites of exposure for metal ENMs. Despite the frequency of exposure of the ocular surface, there is a knowledge gap regarding the effects of metal oxide ENMs on the cornea in health and disease. Therefore, we studied the effects of metal oxide ENMs on the cornea in the presence or absence of injury. Cell viability of immortalized human corneal epithelial (hTCEpi) cells was assessed following treatment with 11 metal oxide ENMs with a concentration ranging from 0.5 to 250 μg/mL for 24 hours. An epithelial wound healing assay with a monolayer of hTCEpi cells was then performed using 11 metal oxide ENMs at select concentrations based on data from the viability assays. Subsequently, based on the in vitro results, in vivo testing of precorneal tear film (PTF) quantity and stability as well as a corneal epithelial wound healing were tested in the presence or absence ZnO or vanadium pentoxide (V2O5) at a concentration of 50 μg/mL. We found that WO3, ZnO, V2O5 and CuO ENMs significantly reduced hTCEpi cell viability in comparison to vehicle control or the other metal oxide ENMs tested. Furthermore, ZnO and V2O5 ENMs also significantly decreased hTCEpi cell migration. Although ZnO and V2O5 did not alter PTF parameters of rabbits in vivo, corneal epithelial wound healing was significantly delayed by topical ZnO while V2O5 did not alter wound healing. Finally, hyperspectral images confirmed penetration of ZnO and V2O5 through all corneal layers and into the iris stroma. Considering the marked epithelial toxicity and corneal penetration of ZnO, further investigations on the impact of this ENM on the eye are warranted.

中文翻译：

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工程金属氧化物纳米材料在体外和体内抑制角膜上皮伤口愈合

眼睛接触金属氧化物工程纳米材料 (ENM) 很常见，例如氧化锌 (ZnO)，它是防晒霜和化妆品的主要成分。包括透明角膜及其保护性泪膜在内的眼表是金属 ENM 的常见暴露部位。尽管眼表暴露的频率很高，但关于金属氧化物 ENM 对角膜健康和疾病的影响仍存在知识空白。因此，我们研究了金属氧化物 ENMs 在有无损伤情况下对角膜的影响。在用浓度范围为 0.5 至 250 μg/mL 的 11 种金属氧化物 ENM 处理 24 小时后，评估了永生化人角膜上皮 (hTCEpi) 细胞的细胞活力。然后使用 11 种金属氧化物 ENM 在选定浓度下使用单层 hTCEpi 细胞进行上皮伤口愈合测定，该测定基于来自活力测定的数据。随后，基于体外结果，在浓度为 50 μg 的 ZnO 或五氧化二钒 (V2O5) 存在或不存在的情况下，测试了角膜前泪膜 (PTF) 数量和稳定性以及角膜上皮伤口愈合的体内测试/毫升。我们发现与载体对照或测试的其他金属氧化物 ENM 相比，WO3、ZnO、V2O5 和 CuO ENM 显着降低了 hTCEpi 细胞活力。此外，ZnO 和 V2O5 ENMs 也显着降低了 hTCEpi 细胞迁移。尽管 ZnO 和 V2O5 没有改变兔体内 PTF 参数，局部 ZnO 显着延迟了角膜上皮伤口愈合，而 V2O5 不会改变伤口愈合。最后，高光谱图像证实 ZnO 和 V2O5 穿透所有角膜层并进入虹膜基质。考虑到 ZnO 显着的上皮毒性和角膜渗透性，有必要进一步研究这种 ENM 对眼睛的影响。