Theodoropoulou, S;
Copland, DA;
Liu, J;
Wu, J;
Gardner, PJ;
Ozaki, E;
Doyle, SL;
... Dick, AD; + view all
(2017)
Interleukin-33 regulates tissue remodelling and inhibits angiogenesis in the eye.
The Journal of Pathology
, 241
(1)
pp. 45-56.
10.1002/path.4816.
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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 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.
| Type: | Article |
|---|---|
| Title: | Interleukin-33 regulates tissue remodelling and inhibits angiogenesis in the eye |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/path.4816 |
| Publisher version: | http://dx.doi.org/10.1002/path.4816 |
| Language: | English |
| Additional information: | Copyright © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
| Keywords: | AMD, IL-33, RPE, angiogenesis, wound healing |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1520028 |
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