title: Interleukin-17A neutralization alleviated ocular neovascularization by promoting M2 and mitigating M1 macrophage polarization.
abstract: Neovascularization (NV), as a cardinal complication of several ocular diseases, has been intensively studied, and research has shown its close association with inflammation and immune cells. In the present study, the role of interleukin-17A (IL-17A) in angiogenesis in the process of ocular NV both in vivo and in vitro was investigated. Also, a paracrine role of IL-17A was demonstrated in the crosstalk between endothelial cells and macrophages in angiogenesis. In the retinas of mice with retinopathy of prematurity, the IL-17A expression increased significantly at postnatal day 15 (P15) and P18 during retinal NV. Mice given IL-17A neutralizing antibody (NAb) developed significantly reduced choroidal NV and retinal NV. Studies on vascular endothelial growth factor (VEGF) over-expressing mice suggested that IL-17A modulated NV through the VEGF pathway. Furthermore, IL-17A deficiency shifted macrophage polarization toward an M2 phenotype during retinal NV with significantly reduced M1 cytokine expression compared with wild-type controls. In vitro assays revealed that IL-17A treated macrophage supernatant gave rise to elevated human umbilical vascular endothelial cell proliferation, tube formation and VEGF receptor 1 and receptor 2 expression. Therefore, IL-17A could potentially serve as a novel target for treating ocular NV diseases. The limitation of this study involved the potential mechanisms, such as which transcription accounted for macrophage polarization and how the subsequent cytokines were modulated when macrophages were polarized. Further studies need to be undertaken to definitively determine the extent to which IL-17A neutralizing anti-angiogenic activity depends on macrophage modulation compared with anti-VEGF treatment.
authors.affiliation: The Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yanji
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: The Department of Ophthalmology, The First People's Hospital, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.affiliation: The Department of Ophthalmology, Presbyterian Hospital-Cornell, New York, NY, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Demetriades
authors.affiliation: The Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Cai
authors.affiliation: The Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yushuo
authors.initials: Y
authors.lastname: Gao
authors.affiliation: The Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ailing
authors.initials: A
authors.lastname: Sui
authors.affiliation: The Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.affiliation: The Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, Shanghai, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Jiang
authors.affiliation: The Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xie
authors.affiliation: Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, Shanghai, China.
authors.forename: Xinghuai
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002460:Cell Line; D020256:Choroidal Neovascularization / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D012160:Retina / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015861:Retinal Neovascularization / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D016207:Cytokines; D018836:Inflammation Mediators; D020381:Interleukin-17; D042461:Vascular Endothelial Growth Factor A
keywords: M1, M2 macrophage polarization; interleukin-17A; ocular neovascularization; vascular endothelial cells; vascular endothelial growth factor