Diabetic retinopathy (DR) is the main cause of visual loss among blinding diseases. The pathological microenvironment, characterized by hypoxia, reactive oxygen species (ROS) accumulation and oxidative stress, is critical to the onset and progression of DR. In this study, an ultrasmall (4–6 nm) copper nanodots was developed as nanozyme (Cu NZs) and dispersed in 2 % Methocel to formulate Cu NZs eye drops to relieve hypoxia and scavenge excrescent ROS for the effective treatment of DR. Due to its smaller size and higher specific surface area, Cu NZs exposes more active sites and can guarantee excellent antioxidant activity. The results of studies indicated that Cu NZs had biocompatible and protective effects on human retinal microvascular endothelial cells (HRMECs), alleviating hypoxia in HRMECs, reducing oxidative stress, and inhibiting hypoxia-inducing factor-1α (HIF-1α)/ vascular endotheliogenesis factor (VEGF) signaling pathway. In an animal model of streptozotocin (STZ)-induced DR, Cu NZs eye drops have been shown to greatly relieve the hypoxic microenvironment of DR and inhibit the expression of HIF-1α and VEGF. CuNZs eye drops reduced inflammatory factors in the DR microenvironment, significantly reducing the progression of neovascularization and vascular leakage. And the nano-enzyme eye drops have no toxic side effects on the eyes and important organs of the whole body. This treatment mode based on the nano enzyme cascade reaction from comprehensive microenvironment regulation (hypoxia relief, free radical scavenging, anti-inflammatory), has excellent ability to treat DR. Although the nanoparticle is effective against DR in the short term at the cellular and animal levels, the long-term efficacy and safety remains to be evaluated.

中文翻译：

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超小铜纳米点滴眼液通过缓解缺氧和抑制HIF-1α/VEGF信号通路调节糖尿病视网膜病变的微环境


糖尿病视网膜病变（DR）是致盲性疾病中导致视力丧失的主要原因。以缺氧、活性氧（ROS）积累和氧化应激为特征的病理微环境对于 DR 的发生和进展至关重要。在本研究中，开发了一种超小（4-6 nm）铜纳米点作为纳米酶（Cu NZs），并将其分散在 2% Methocel 中配制 Cu NZs 滴眼剂，以缓解缺氧并清除多余的 ROS，从而有效治疗 DR。由于其较小的尺寸和较高的比表面积，Cu NZs 暴露出更多的活性位点，可以保证优异的抗氧化活性。研究结果表明，Cu NZs对人视网膜微血管内皮细胞（HRMECs）具有生物相容性和保护作用，缓解HRMECs缺氧，减轻氧化应激，抑制缺氧诱导因子1α（HIF-1α）/血管内皮生成因子（ VEGF）信号通路。在链脲佐菌素（STZ）诱导的 DR 动物模型中，Cu NZs 滴眼液被证明可以极大地缓解 DR 的缺氧微环境，并抑制 HIF-1α 和 VEGF 的表达。 CuNZs 滴眼液可减少 DR 微环境中的炎症因子，显着减少新生血管形成和血管渗漏的进展。并且纳米酶滴眼液对眼睛及全身重要器官无毒副作用。这种基于纳米酶级联反应的综合微环境调节（缓解缺氧、清除自由基、抗炎）的治疗模式，具有优异的治疗DR的能力。尽管纳米颗粒在细胞和动物水平上短期内可有效对抗 DR，但其长期疗效和安全性仍有待评估。