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载纳米氧化铈的可注射水凝胶治疗光诱导 Nrf2 小鼠年龄相关性黄斑变性

Light-induced Nrf2 mice as atrophic age-related macular degeneration model and treatment with nanoceria laden injectable hydrogel.

机构信息

Department of Ophthalmology, the University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

Carolina Institute for Nano Medicine, the University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

出版信息

Sci Rep. 2019 Oct 10;9(1):14573. doi: 10.1038/s41598-019-51151-7.

Abstract

Elevated oxidative stress and associated reactive oxygen species (ROS) accumulation are hallmarks in the induction and progression of age-related macular degeneration (AMD). By exposing nuclear factor erythroid 2-related factor (Nrf2) knockout (Nrf2) mice to mild white light, we were able to generate a new dry-AMD like murine model to the study. This animal model developed phenotypes of photoreceptor degeneration, retinal function impairment, ROS accumulation, and inflammation reaction in a relatively shorter time. In the treatment of this animal model we utilized an antioxidative and water soluble nanoparticle known as glycol chitosan coated cerium oxide nanoparticles (GCCNP). The delivery of GCCNP protected retina against progressive retinal oxidative damage. Further combination of GCCNP with alginate-gelatin based injectable hydrogel provided synergistic antioxidant effects and achieved a more rapid recovery of the retinal pigment epithelium and photoreceptor cells. This combined treatment technique has the potential to translate into a clinical intervention for the treatment of AMD.

摘要

氧化应激增加和相关活性氧(ROS)积累是与年龄相关的黄斑变性(AMD)的诱导和进展相关的特征。通过使核因子红细胞 2 相关因子(Nrf2)敲除(Nrf2)小鼠暴露于轻度白光下,我们能够生成一种新的干性 AMD 样的小鼠模型进行研究。该动物模型在相对较短的时间内发展出光感受器变性、视网膜功能障碍、ROS 积累和炎症反应的表型。在该动物模型的治疗中,我们利用了一种抗氧化且水溶性的纳米颗粒,即壳聚糖修饰的氧化铈纳米颗粒(GCCNP)。GCCNP 的递送可防止视网膜受到进行性氧化损伤。进一步将 GCCNP 与藻酸盐-明胶基可注射水凝胶结合使用可提供协同抗氧化作用,并实现视网膜色素上皮和光感受器细胞的更快恢复。这种联合治疗技术有可能转化为 AMD 的临床干预措施。

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