title: Neutralization of IL-23 depresses experimental ocular neovascularization.
abstract: Interleukin-23 (IL-23) is a heterodimeric cytokine that consists of p19, a novel subunit, and p40, which is shared by IL-12. IL-23 has been demonstrated to play an important role in autoimmunity and tumor growth. However, the role of IL-23 in ocular neovascularization (NV) diseases remains unclear. In this study, we explored the role of IL-23 in the processing of retinal and choroidal neovascularization (RNV and CNV). We found a significantly higher expression of IL-23 in the retinas with oxygen-induced retinopathy (OIR), and after neutralizing IL-23, the mRNA and protein levels of the angiogenic factors vascular endothelial growth factor receptor (VEGFR)1/FLT-1, VEGFR2/FLK-1, placental growth factor (PIGF), endothelial-specific receptor tyrosine kinase (Tie2), inducible nitric-oxide synthase (iNOS), matrix metalloproteinase (MMP) 2 and MMP9 were significantly down regulated, while the opposite trend was found for the anti-angiogenic molecules chemokine (C-X-C motif) ligand (CXCL) 9 and CXCL10. IL-23 blockade caused less NV in both the RNV and CNV mouse models. In addition, our in vitro assay showed that IL-23 alone is able to increase the ability of endothelial cells to form tubes. Our findings suggest that targeting IL-23 could be a potential therapy for RNV and CNV diseases.
authors.affiliation: The Department of Ophthalmology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Cai
authors.affiliation: The Department of Ophthalmology, The First People's Hospital, The Third Affiliated Hospital of Zunyi Medical University, 98 Fenghuang Road, Zunyi, Guizhou, 563002, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.affiliation: The Department of Ophthalmology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Shen
authors.affiliation: The Department of Ophthalmology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China.
authors.forename: Yanji
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: The Department of Ophthalmology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China.
authors.forename: Yushuo
authors.initials: Y
authors.lastname: Gao
authors.affiliation: The Department of Ophthalmology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China.
authors.forename: Ailing
authors.initials: A
authors.lastname: Sui
authors.affiliation: The Department of Ophthalmology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.affiliation: The Department of Ophthalmology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China. Electronic address: yszhong68@126.com.
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: The Department of Ophthalmology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025, China. Electronic address: bingxie1@gmail.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Xie
mesh_terms: D000704:Analysis of Variance; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D018925:Chemokines / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D053759:Interleukin-23 / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D015861:Retinal Neovascularization / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D043925:Angiogenesis Inducing Agents; D018925:Chemokines; D053759:Interleukin-23; D012333:RNA, Messenger
keywords: Angiogenic factors; Interleukin-23; Ocular neovascularization; Tube formation