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

光诱导 Nrf2-/- 小鼠作为萎缩性年龄相关性黄斑变性模型并用载有纳米二氧化铈的可注射水凝胶治疗

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作者:Kai Wang, Min Zheng, Kaitlyn Lee Lester, Zongchao Han

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.

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