Abstract：
Dry eye disease (DED) affects a substantial worldwide population with increasing frequency. Current single-targeting DED management is severely hindered by the existence of an oxidative stress-inflammation vicious cycle and complicated intercellular crosstalk within the ocular microenvironment. Here, a nanozyme-based eye drop, namely nanoceria loading cyclosporin A (Cs@P/CeO2), is developed, which possesses long-term antioxidative and anti-inflammatory capacities due to its regenerative antioxidative activity and sustained release of cyclosporin A (CsA). In vitro studies showed that the dual-functional Cs@P/CeO2 not only inhibits cellular reactive oxygen species production, sequentially maintaining mitochondrial integrity, but also downregulates inflammatory processes and repolarizes macrophages. Moreover, using flow cytometric and single-cell sequencing data, the in vivo therapeutic effect of Cs@P/CeO2 was systemically demonstrated, which rebalances the immune-epithelial communication in the corneal microenvironment with less inflammatory macrophage polarization, restrained oxidative stress, and enhanced epithelium regeneration. Collectively, our data proved that the antioxidative and anti-inflammatory Cs@P/CeO2 may provide therapeutic insights into DED management.
摘要：
干眼病(DED)以越来越高的频率影响大量的全球人口。目前的单靶向DED管理受到眼微环境中氧化应激-炎症恶性循环和复杂细胞间串扰的存在的严重阻碍。这里,一种基于纳米酶的滴眼液，即纳米氧化铈负载环孢菌素A(Cs@P/CeO2)，被开发,由于其再生抗氧化活性和环孢菌素A（CsA）的持续释放，具有长期抗氧化和抗炎能力。体外研究表明，双功能Cs@P/CeO2不仅抑制细胞活性氧的产生，依次维持线粒体的完整性，但也下调炎症过程并使巨噬细胞复极化。此外，使用流式细胞仪和单细胞测序数据，系统证明了Cs@P/CeO2的体内治疗效果，重新平衡角膜微环境中的免疫-上皮通讯，减少炎症巨噬细胞极化，抑制氧化应激，和增强上皮再生。总的来说，我们的数据证明抗氧化和抗炎Cs@P/CeO2可以为DED管理提供治疗见解.
