IL-17A mediates inflammation-related retinal pigment epithelial cells injury via ERK signaling pathway
Authors:   Department of Ophthalmology, Shanghai General Hospital (Shanghai First People&#x2019;s Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China; National Clinical Research Center for Ophthalmic Diseases, Shanghai 200080, China; National Clinical Research Center for Eye Diseases, Shanghai 200080, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai 200080, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai 200080, China, Zhong Hui-Min , Chen Yu-Hong ,   Department of Ophthalmology, Shanghai General Hospital (Shanghai First People&#x2019;s Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China; National Clinical Research Center for Ophthalmic Diseases, Shanghai 200080, China; National Clinical Research Center for Eye Diseases, Shanghai 200080, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai 200080, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai 200080, China, Zhao Xiao-Huan ,   Department of Ophthalmology, Shanghai General Hospital (Shanghai First People&#x2019;s Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China; National Clinical Research Center for Ophthalmic Diseases, Shanghai 200080, China; National Clinical Research Center for Eye Diseases, Shanghai 200080, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai 200080, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai 200080, China, Huang Xiao-Xu ,   Department of Ophthalmology, Shanghai General Hospital (Shanghai First People&#x2019;s Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China; National Clinical Research Center for Ophthalmic Diseases, Shanghai 200080, China; National Clinical Research Center for Eye Diseases, Shanghai 200080, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai 200080, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai 200080, China, Zhou Min-Wen ,   Department of Ophthalmology, Shanghai General Hospital (Shanghai First People&#x2019;s Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China; National Clinical Research Center for Ophthalmic Diseases, Shanghai 200080, China; National Clinical Research Center for Eye Diseases, Shanghai 200080, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai 200080, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai 200080, China, Sun Xiao-Dong ,   Department of Ophthalmology, Shanghai General Hospital (Shanghai First People&#x2019;s Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China; National Clinical Research Center for Ophthalmic Diseases, Shanghai 200080, China; National Clinical Research Center for Eye Diseases, Shanghai 200080, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai 200080, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai 200080, China
Published: December 2024

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).

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.