title: Interleukin-33 regulates tissue remodelling and inhibits angiogenesis in the eye.
abstract: Age-related macular degeneration (AMD) is the leading cause of central vision loss worldwide. Loss of retinal pigment epithelium (RPE) is a major pathological hallmark in AMD with or without pathological neovascularization. Although activation of the immune system is implicated in disease progression, pathological pathways remain diverse and unclear. Here, we report an unexpected protective role of a pro-inflammatory cytokine, interleukin-33 (IL-33), in ocular angiogenesis. IL-33 and its receptor (ST2) are expressed constitutively in human and murine retina and choroid. When RPE was activated, IL-33 expression was markedly elevated in vitro. We found that IL-33 regulated tissue remodelling by attenuating wound-healing responses, including reduction in the migration of choroidal fibroblasts and retinal microvascular endothelial cells, and inhibition of collagen gel contraction. In vivo, local administration of recombinant IL-33 inhibited murine choroidal neovascularization (CNV) formation, a surrogate of human neovascular AMD, and this effect was ST2-dependent. Collectively, these data demonstrate IL-33 as a potential immunotherapy and distinguishes pathways for subverting AMD pathology. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
authors.affiliation: Academic Unit of Ophthalmology, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Sofia
authors.initials: S
authors.lastname: Theodoropoulou
authors.affiliation: Academic Unit of Ophthalmology, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Copland
authors.affiliation: Academic Unit of Ophthalmology, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Academic Unit of Ophthalmology, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Wu
authors.affiliation: University College London-Institute of Ophthalmology, London, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gardner
authors.affiliation: Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: Ema
authors.initials: E
authors.lastname: Ozaki
authors.affiliation: Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Doyle
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
authors.forename: Matthew
authors.initials: M
authors.lastname: Campbell
authors.affiliation: Academic Unit of Ophthalmology, School of Clinical Sciences, University of Bristol, Bristol, UK.|University College London-Institute of Ophthalmology, London, UK.|National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London, UK.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Dick
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D002829:Choroid / Q000276:immunology; D020256:Choroidal Neovascularization / Q000188:drug therapy / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000378:metabolism; D000067596:Interleukin-33 / Q000276:immunology* / Q000627:therapeutic use; D008268:Macular Degeneration / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D055213:Retinal Pigment Epithelium / Q000276:immunology; D055815:Young Adult
chemical_list: C079241:IL1RL1 protein, human; C506536:IL33 protein, human; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D011994:Recombinant Proteins
keywords: AMD; IL-33; RPE; angiogenesis; wound healing