Repeated Topical Administration of 3 nm Cerium Oxide Nanoparticles Reverts Disease Atrophic Phenotype and Arrests Neovascular Degeneration in AMD Mouse Models
Repeated Topical Administration of 3 nm Cerium Oxide Nanoparticles Reverts Disease Atrophic Phenotype and Arrests Neovascular Degeneration in AMD Mouse Models
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DOI：
10.1021/acsnano.2c05447
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发表时间：
2023-01-03
期刊：
影响因子：
17.1
通讯作者：
Garcia-Arumi, Josep
中科院分区：
文献类型：
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作者：
Badia, Anna;Duarri, Anna;Garcia-Arumi, Josep
视网膜和视网膜色素上皮氧化应激增加与老年性黄斑变性(AMD)有关。抗氧化剂氧化铈纳米颗粒(CeO(2)NPs)已被用于治疗动物模型中的视网膜退行性病变，尽管它们的递送路线对于慢性患者的治疗并不理想。在这项工作中，我们制备了一种眼部局部给药的配方，它含有小的(3 Nm)、非聚集的生物相容的CeO(2)纳米粒。体外实验结果表明，CeO(2)纳米粒子具有良好的生物相容性和保护性，可降低ARPE19细胞的氧化应激，抑制HUVEC和体外新生血管生长模型中与病理性血管生成相关的新生血管形成。在体内实验中，我们观察了局部给药后CeO(2)NPs到达视网膜的能力，以及随后视网膜退化模型DKOrd8改变的视网膜转录组恢复到健康对照组小鼠的能力，以及炎症减轻和变性停止的迹象。此外，CeO2NP滴眼液的治疗通过降低血管内皮生长因子和增加PEDF水平来减少激光诱导的小鼠脉络膜新生血管损伤。这些结果表明CeO2NP滴眼液对干性和湿性AMD疾病都是一种有益的抗氧化剂和神经保护治疗。
Increased oxidative stress in the retina and retinal pigment epithelium is implicated in age-related macular degeneration (AMD). Antioxidant cerium oxide nanoparticles (CeO(2)NPs) have been used to treat degenerative retinal pathologies in animal models, although their delivery route is not ideal for chronic patient treatment. In this work, we prepared a formulation for ocular topical delivery that contains small (3 nm), nonaggregated biocompatible CeO(2)NPs. In vitro results indicate the biocompatible and protective character of the CeO(2)NPs, reducing oxidative stress in ARPE19 cells and inhibiting neovascularization related to pathological angiogenesis in both HUVEC and in in vitro models of neovascular growth. In the in vivo experiments, we observed the capacity of CeO(2)NPs to reach the retina after topical delivery and a subsequent reversion of the altered retinal transcriptome of the retinal degenerative mouse model DKOrd8 toward that of healthy control mice, together with signs of decreased inflammation and arrest of degeneration. Furthermore, CeO2NP eye drops' treatment reduced laser-induced choroidal neovascular lesions in mice by lowering VEGF and increasing PEDF levels. These results indicate that CeO2NP eye drops are a beneficial antioxidant and neuroprotective treatment for both dry and wet forms of AMD disease.