Retinal Microenvironment-Protected Rhein-GFFYE Nanofibers Attenuate Retinal Ischemia-Reperfusion Injury via Inhibiting Oxidative Stress and Regulating Microglial/Macrophage M1/M2 Polarization.
Retinal Microenvironment-Protected Rhein-GFFYE Nanofibers Attenuate Retinal Ischemia-Reperfusion Injury via Inhibiting Oxidative Stress and Regulating Microglial/Macrophage M1/M2 Polarization.
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DOI：
10.1002/advs.202302909
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发表时间：
2023-10
期刊：
影响因子：
15.1
通讯作者：
Yang, Zhimou
中科院分区：
文献类型：
--
作者：
Zhang, Zhuhong;Peng, Shengjun;Xu, Tengyan;Liu, Jia;Zhao, Laien;Xu, Hui;Zhang, Wen;Zhu, Yuanying;Yang, Zhimou
关键词：
视网膜缺血参与了多种眼科疾病的发生和发展，包括青光眼、糖尿病视网膜病变和视网膜中央动脉阻塞。据我们所知，很少有研究报道自组装肽天然产物可以抑制眼部炎症和氧化应激。本文设计合成了一种能够将大黄酸的非亲水性转化为两亲性缓释治疗剂的自组装肽GFFYE，并构建了大黄酸治疗纳米纤维(简称Rh-GFFYE)，用于治疗视网膜缺血再灌注(RIR)损伤。重组人GFFYE可显著改善体外缺氧-葡萄糖剥夺(OGD)视网膜缺血模型和RIR损伤大鼠模型的氧化应激和炎症反应。重组人GFFYE还能显著促进视网膜电生理恢复，并表现出良好的生物相容性。重要的是，rh-GFFYE还促进了M1型巨噬细胞向M2型巨噬细胞的转变，最终改变了促炎微环境。进一步的治疗机制研究表明，rh-GFFYE激活PI3K/κ/mTOR信号通路以减少氧化应激，抑制NF-AktB和STAT3信号通路影响炎症和巨噬细胞极化。总之，负载大黄酸的纳米平台通过调节视网膜微环境减轻了RIR损伤。这一发现有望促进疏水天然产品在RIR损伤相关眼病中的临床应用。目前视网膜缺血相关疾病的临床治疗主要集中在单一的病理机制上。尽管大黄酸具有抗炎和抗氧化的药理活性，但其非亲水性限制了其潜在的临床应用。本研究构建了一个基于多肽的大黄酸纳米平台，并提出它可以通过调节视网膜微环境来减轻RIR损伤。
Retinal ischemia is involved in the occurrence and development of various eye diseases, including glaucoma, diabetic retinopathy, and central retinal artery occlusion. To the best of our knowledge, few studies have reported self‐assembling peptide natural products for the suppression of ocular inflammation and oxidative stress. Herein, a self‐assembling peptide GFFYE is designed and synthesized, which can transform the non‐hydrophilicity of rhein into an amphiphilic sustained‐release therapeutic agent, and rhein‐based therapeutic nanofibers (abbreviated as Rh‐GFFYE) are constructed for the treatment of retinal ischemia‐reperfusion (RIR) injury. Rh‐GFFYE significantly ameliorates oxidative stress and inflammation in an in vitro oxygen‐glucose deprivation (OGD) model of retinal ischemia and a rat model of RIR injury. Rh‐GFFYE also significantly enhances retinal electrophysiological recovery and exhibits good biocompatibility. Importantly, Rh‐GFFYE also promotes the transition of M1‐type macrophages to the M2 type, ultimately altering the pro‐inflammatory microenvironment. Further investigation of the treatment mechanism indicates that Rh‐GFFYE activates the PI3K/AKT/mTOR signaling pathway to reduce oxidative stress and inhibits the NF‐κB and STAT3 signaling pathways to affect inflammation and macrophage polarization. In conclusion, the rhein‐loaded nanoplatform alleviates RIR injury by modulating the retinal microenvironment. The findings are expected to promote the clinical application of hydrophobic natural products in RIR injury‐associated eye diseases. Current clinical treatments for retinal ischemia‐related diseases focus on a single pathological mechanism. Despite the anti‐inflammatory and antioxidant pharmacological activities of rhein, its non‐hydrophilicity limits the potential clinical application. This study constructs a peptide‐based rhein nanoplatform and proposes that it can alleviate RIR injury by modulating the retinal microenvironment.
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影响因子：
7.3
作者：
通讯作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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