{"title":"IL-17A mediates inflammation-related retinal pigment epithelial cells injury <i>via</i> ERK signaling pathway.","authors":"Hui-Min Zhong, Bing-Qiao Shen, Yu-Hong Chen, Xiao-Huan Zhao, Xiao-Xu Huang, Min-Wen Zhou, Xiao-Dong Sun","doi":"10.18240/ijo.2025.01.03","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>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).</p><p><strong>Mrthods: </strong>A sodium iodate (NaIO<sub>3</sub>) mouse model as well as <i>IL-17A</i> <sup>-/-</sup> mice were established. The effects of inflammatory cytokines in RPE cells and retinal microglia before and after NaIO<sub>3</sub> modeling <i>in vivo</i> and <i>in vitro</i>, 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.</p><p><strong>Results: </strong>In the scenario of NaIO<sub>3</sub> stimulation, RPE cells obviously tended to degenerate. Simultaneously proliferation and activation of retinal microglia was confirmed in NaIO<sub>3</sub>-stimulated mice, whereas such effects induced by NaIO<sub>3</sub> were significantly ameliorated with IL-17A NAb intervention or in <i>IL-17A</i> <sup>-/-</sup> 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<sub>3</sub>-induced damage in RPE cells <i>in vivo</i> and <i>ex vivo</i>. Meanwhile, the extracellular signal-regulated kinase (ERK) signaling pathway was shown to be participated in the regulation of NaIO<sub>3</sub>-induced RPE cells injury mediated by IL-17A <i>in vivo</i> and <i>ex vivo</i>, as IL-17A-induced inflammatory cytokines release in the NaIO<sub>3</sub> model was alleviated after blocking the ERK pathway.</p><p><strong>Conclusion: </strong>IL-17A probably promotes the NaIO<sub>3</sub>-induced RPE cells injury through exacerbating inflammation in terms of retinal microglia activation and inflammatory cytokines release <i>via</i> ERK signaling pathway. Inhibition of IL-17A may be a new potential target for dry AMD treatment.</p>","PeriodicalId":14312,"journal":{"name":"International journal of ophthalmology","volume":"18 1","pages":"15-27"},"PeriodicalIF":1.9000,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672097/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International journal of ophthalmology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.18240/ijo.2025.01.03","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Aim: 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).
Mrthods: A sodium iodate (NaIO3) mouse model as well as IL-17A-/- mice were established. The effects of inflammatory cytokines in RPE cells and retinal microglia before and after NaIO3 modeling in vivo and in vitro, 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.
Results: In the scenario of NaIO3 stimulation, RPE cells obviously tended to degenerate. Simultaneously proliferation and activation of retinal microglia was confirmed in NaIO3-stimulated mice, whereas such effects induced by NaIO3 were significantly ameliorated with IL-17A NAb intervention or in IL-17A-/- mice. In addition, IL-17A promoted the proliferation and activation of microglia as well as oxidative damage and the secretion of inflammatory cytokines alongside NaIO3-induced damage in RPE cells in vivo and ex vivo. Meanwhile, the extracellular signal-regulated kinase (ERK) signaling pathway was shown to be participated in the regulation of NaIO3-induced RPE cells injury mediated by IL-17A in vivo and ex vivo, as IL-17A-induced inflammatory cytokines release in the NaIO3 model was alleviated after blocking the ERK pathway.
Conclusion: IL-17A probably promotes the NaIO3-induced RPE cells injury through exacerbating inflammation in terms of retinal microglia activation and inflammatory cytokines release via ERK signaling pathway. Inhibition of IL-17A may be a new potential target for dry AMD treatment.
期刊介绍：
· International Journal of Ophthalmology-IJO (English edition) is a global ophthalmological scientific publication
and a peer-reviewed open access periodical (ISSN 2222-3959 print, ISSN 2227-4898 online).
This journal is sponsored by Chinese Medical Association Xi’an Branch and obtains guidance and support from
WHO and ICO (International Council of Ophthalmology). It has been indexed in SCIE, PubMed,
PubMed-Central, Chemical Abstracts, Scopus, EMBASE , and DOAJ. IJO JCR IF in 2017 is 1.166.
IJO was established in 2008, with editorial office in Xi’an, China. It is a monthly publication. General Scientific
Advisors include Prof. Hugh Taylor (President of ICO); Prof.Bruce Spivey (Immediate Past President of ICO);
Prof.Mark Tso (Ex-Vice President of ICO) and Prof.Daiming Fan (Academician and Vice President,
Chinese Academy of Engineering.
International Scientific Advisors include Prof. Serge Resnikoff (WHO Senior Speciatist for Prevention of
blindness), Prof. Chi-Chao Chan (National Eye Institute, USA) and Prof. Richard L Abbott (Ex-President of
AAO/PAAO) et al.
Honorary Editors-in-Chief: Prof. Li-Xin Xie(Academician of Chinese Academy of
Engineering/Honorary President of Chinese Ophthalmological Society); Prof. Dennis Lam (President of APAO) and
Prof. Xiao-Xin Li (Ex-President of Chinese Ophthalmological Society).
Chief Editor: Prof. Xiu-Wen Hu (President of IJO Press).
Editors-in-Chief: Prof. Yan-Nian Hui (Ex-Director, Eye Institute of Chinese PLA) and
Prof. George Chiou (Founding chief editor of Journal of Ocular Pharmacology & Therapeutics).
Associate Editors-in-Chief include:
Prof. Ning-Li Wang (President Elect of APAO);
Prof. Ke Yao (President of Chinese Ophthalmological Society) ;
Prof.William Smiddy (Bascom Palmer Eye instituteUSA) ;
Prof.Joel Schuman (President of Association of University Professors of Ophthalmology,USA);
Prof.Yizhi Liu (Vice President of Chinese Ophtlalmology Society);
Prof.Yu-Sheng Wang (Director of Eye Institute of Chinese PLA);
Prof.Ling-Yun Cheng (Director of Ocular Pharmacology, Shiley Eye Center, USA).
IJO accepts contributions in English from all over the world. It includes mainly original articles and review articles,
both basic and clinical papers.
Instruction is Welcome Contribution is Welcome Citation is Welcome
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International Council of Ophthalmology(ICO), PubMed, PMC, American Academy of Ophthalmology, Asia-Pacific, Thomson Reuters, The Charlesworth Group, Crossref,Scopus,Publons, DOAJ etc.
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