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Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model

Research output: Contribution to journalArticle

  • Colin J Chu
  • Peter J Gardner
  • David A Copland
  • Sidath E Liyanage
  • Anai Gonzalez-Cordero
  • Sophia-Martha Kleine Holthaus
  • Ulrich F O Luhmann
  • Alexander J Smith
  • Robin R Ali
  • Andrew D Dick
Original languageEnglish
Pages (from-to)473-81
Number of pages9
JournalDisease Models and Mechanisms
Volume9
Issue number4
DOIs
DateAccepted/In press - 20 Jan 2016
DatePublished (current) - 5 Apr 2016

Abstract

Endotoxin-induced uveitis (EIU) in rodents is a model of acute Toll-like receptor 4 (TLR4)-mediated organ inflammation, and has been used to model human anterior uveitis, examine leukocyte trafficking and test novel anti-inflammatory therapeutics. Wider adoption has been limited by the requirement for manual, non-specific, cell-count scoring of histological sections from each eye as a measure of disease severity. Here, we describe a comprehensive and efficient technique that uses ocular dissection and multimodal tissue analysis. This allows matched disease scoring by multicolour flow cytometric analysis of the inflammatory infiltrate, protein analysis on ocular supernatants and qPCR on remnant tissues of the same eye. Dynamic changes in cell populations could be identified and mapped to chemokine and cytokine changes over the course of the model. To validate the technique, dose-responsive suppression of leukocyte infiltration by recombinant interleukin-10 was demonstrated, as well as selective suppression of the monocyte (CD11b+Ly6C+) infiltrate, in mice deficient for eitherCcl2orCcr2 Optical coherence tomography (OCT) was used for the first time in this model to allowin vivoimaging of infiltrating vitreous cells, and correlated with CD11b+Ly6G+ counts to provide another unique measure of cell populations in the ocular tissue. Multimodal tissue analysis of EIU is proposed as a new standard to improve and broaden the application of this model.

    Research areas

  • EIU, Flow cytometry, OCT

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via The Company of Biologists Ltd at 10.1242/dmm.022475. Please refer to any applicable terms of use of the publisher.

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    Licence: CC BY

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