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Interleukin-33 regulates tissue remodelling and inhibits angiogenesis in the eye

Theodoropoulou, Sofia, Copland, David A, Liu, Jian, Wu, Jiahui, Gardner, Peter J, Ozaki, Ema, Doyle, Sarah L, Campbell, Matthew and Dick, Andrew D (2016) Interleukin-33 regulates tissue remodelling and inhibits angiogenesis in the eye. The Journal of Pathology, 241 (1). pp. 45-56. ISSN 0022-3417

Item Type: Article

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.

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Depositing User: Matthew Campbell

Identifiers

Item ID: 13135
Identification Number: https://doi.org/10.1002/path.4816
ISSN: 0022-3417
URI: http://sure.sunderland.ac.uk/id/eprint/13135
Official URL: http://dx.doi.org/10.1002/path.4816

Users with ORCIDS

ORCID for Matthew Campbell: ORCID iD orcid.org/0000-0001-5883-5041

Catalogue record

Date Deposited: 15 Feb 2021 12:02
Last Modified: 15 Feb 2021 12:15

Contributors

Author: Matthew Campbell ORCID iD
Author: Sofia Theodoropoulou
Author: David A Copland
Author: Jian Liu
Author: Jiahui Wu
Author: Peter J Gardner
Author: Ema Ozaki
Author: Sarah L Doyle
Author: Andrew D Dick

University Divisions

Faculty of Health Sciences and Wellbeing

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