Palacka Katerina, Hermankova Barbora, Cervena Tereza, Rossner Pavel, Zajicova Alena, Uherkova Eva, Holan Vladimir, Javorkova Eliska
Department of Toxicology and Molecular Epidemiology, Institute of Experimental Medicine of the Czech Academy of Sciences, 142 20, Prague 4, Czech Republic.
Department of Cell Biology, Faculty of Science, Charles University, 128 43, Prague 2, Czech Republic.
Inflammation. 2024 Aug 27. doi: 10.1007/s10753-024-02128-w.
Activation of immune response plays an important role in the development of retinal diseases. One of the main populations of immune cells contributing to the retinal homeostasis are microglia, which represent a population of residential macrophages. However, under pathological conditions, microglia become activated and rather support a harmful inflammatory reaction and retinal angiogenesis. Therefore, targeting these cells could provide protection against retinal neuroinflammation and neovascularization. In the recent study, we analyzed effects of silver nanoparticles (AgNPs) on microglia in vitro and in vivo. We showed that the AgNPs interact in vitro with stimulated mouse CD45/CD11b positive cells (microglia/macrophages), decrease their secretion of nitric oxide and vascular endothelial growth factor, and regulate the expression of genes for Iba-1 and interleukin-1β (IL-1β). In our in vivo experimental mouse model, the intravitreal application of a mixture of proinflammatory cytokines tumor necrosis factor-α, IL-1β and interferon-γ induced local inflammation and increased local expression of genes for inducible nitric oxide synthase, IL-α, IL-1β and galectin-3 in the retina. This stimulation of local inflammatory reaction was significantly inhibited by intravitreal administration of AgNPs. The application of AgNPs also decreased the presence of CD11b/Galectin-3 positive cells in neuroinflammatory retina, but did not influence viability of cells and expression of gene for rhodopsin in the retinal tissue. These data indicate that AgNPs regulate reactivity of activated microglia in the diseased retina and thus could provide a beneficial effect for the treatment of several retinal diseases.
免疫反应的激活在视网膜疾病的发展中起着重要作用。对维持视网膜内环境稳态起作用的主要免疫细胞群体之一是小胶质细胞，它是一群驻留巨噬细胞。然而，在病理条件下，小胶质细胞会被激活，反而会促进有害的炎症反应和视网膜血管生成。因此，靶向这些细胞可以预防视网膜神经炎症和新生血管形成。在最近的研究中，我们分析了银纳米颗粒（AgNPs）在体外和体内对小胶质细胞的影响。我们发现，AgNPs在体外与受刺激的小鼠CD45/CD11b阳性细胞（小胶质细胞/巨噬细胞）相互作用，减少它们一氧化氮和血管内皮生长因子的分泌，并调节Iba-1和白细胞介素-1β（IL-1β）基因的表达。在我们的体内实验小鼠模型中，玻璃体内注射促炎细胞因子肿瘤坏死因子-α、IL-1β和干扰素-γ的混合物会诱导局部炎症，并增加视网膜中诱导型一氧化氮合酶、IL-α、IL-1β和半乳糖凝集素-3基因的局部表达。玻璃体内注射AgNPs可显著抑制这种局部炎症反应的刺激。AgNPs的应用还减少了神经炎症性视网膜中CD11b/半乳糖凝集素-3阳性细胞的存在，但不影响细胞活力和视网膜组织中视紫红质基因的表达。这些数据表明，AgNPs可调节患病视网膜中活化小胶质细胞的反应性，因此可能对几种视网膜疾病的治疗产生有益效果。
