Zhong Hui-Min, Shen Bing-Qiao, Chen Yu-Hong, Zhao Xiao-Huan, Huang Xiao-Xu, Zhou Min-Wen, Sun Xiao-Dong
Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China.
National Clinical Research Center for Ophthalmic Diseases, Shanghai 200080, China.
Int J Ophthalmol. 2025 Jan 18;18(1):15-27. doi: 10.18240/ijo.2025.01.03. eCollection 2025.
To investigate whether interleukin-17A (IL-17A) gets involved in the mechanisms of inflammation-related retinal pigment epithelium (RPE) cells injury and its significance in age-related macular degeneration (AMD).
A sodium iodate (NaIO) mouse model as well as mice were established. The effects of inflammatory cytokines in RPE cells and retinal microglia before and after NaIO modeling and , were investigated using immunofluorescence, immunoprotein blotting, and quantitative real-time fluorescence polymerase chain reaction (qRT-PCR), respectively. Interventions using recombinant IL-17A protein (rIL-17A) or IL-17A neutralizing antibody (IL-17A NAb) were used to observe the subsequent differences in fundus, fundus photography and optical coherence tomography (OCT), cell viability, and expression of oxidative stress-related markers before and after modeling, and to screen for key signaling pathways.
In the scenario of NaIO stimulation, RPE cells obviously tended to degenerate. Simultaneously proliferation and activation of retinal microglia was confirmed in NaIO-stimulated mice, whereas such effects induced by NaIO were significantly ameliorated with IL-17A NAb intervention or in mice. In addition, IL-17A promoted the proliferation and activation of microglia as well as oxidative damage and the secretion of inflammatory cytokines alongside NaIO-induced damage in RPE cells and . Meanwhile, the extracellular signal-regulated kinase (ERK) signaling pathway was shown to be participated in the regulation of NaIO-induced RPE cells injury mediated by IL-17A and , as IL-17A-induced inflammatory cytokines release in the NaIO model was alleviated after blocking the ERK pathway.
IL-17A probably promotes the NaIO-induced RPE cells injury through exacerbating inflammation in terms of retinal microglia activation and inflammatory cytokines release ERK signaling pathway. Inhibition of IL-17A may be a new potential target for dry AMD treatment.
研究白细胞介素-17A（IL-17A）是否参与炎症相关视网膜色素上皮（RPE）细胞损伤机制及其在年龄相关性黄斑变性（AMD）中的意义。
建立碘酸钠（NaIO）小鼠模型以及 小鼠模型。分别采用免疫荧光、免疫蛋白印迹和定量实时荧光聚合酶链反应（qRT-PCR）研究NaIO建模前后RPE细胞和视网膜小胶质细胞中炎性细胞因子的作用。使用重组IL-17A蛋白（rIL-17A）或IL-17A中和抗体（IL-17A NAb）进行干预，观察建模前后眼底、眼底照相和光学相干断层扫描（OCT）、细胞活力以及氧化应激相关标志物表达的后续差异，并筛选关键信号通路。
在NaIO刺激的情况下，RPE细胞明显趋于退化。同时，在NaIO刺激的小鼠中证实视网膜小胶质细胞增殖和活化，而IL-17A NAb干预或在 小鼠中，NaIO诱导的此类效应得到显著改善。此外，IL-17A促进小胶质细胞的增殖和活化以及氧化损伤，并在NaIO诱导的RPE细胞损伤和 中促进炎性细胞因子的分泌。同时，细胞外信号调节激酶（ERK）信号通路参与由IL-17A介导的NaIO诱导的RPE细胞损伤的调节，因为在阻断ERK通路后，NaIO模型中IL-17A诱导的炎性细胞因子释放得到缓解。
IL-17A可能通过加剧视网膜小胶质细胞活化和炎性细胞因子释放方面的炎症来促进NaIO诱导的RPE细胞损伤 ERK信号通路。抑制IL-17A可能是干性AMD治疗的新潜在靶点。
