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

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

Research output: Contribution to journalArticle (Academic Journal)

22 Citations (Scopus)
369 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)45–56
Number of pages12
JournalJournal of Pathology
Volume241
Issue number1
Early online date16 Nov 2016
DOIs
Publication statusPublished - 16 Dec 2016

Keywords

  • IL-33
  • AMD
  • RPE
  • angiogenesis
  • wound healing

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