Chu, CJ;
Gardner, PJ;
Copland, DA;
Liyanage, SE;
Gonzalez-Cordero, A;
Kleine Holthaus, SM;
Luhmann, UF;
... Dick, AD; + view all
(2016)
Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model.
Disease Models and Mechanisms
, 9
(4)
pp. 473-481.
10.1242/dmm.022475.
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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.
| Type: | Article |
|---|---|
| Title: | Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1242/dmm.022475 |
| Publisher version: | http://dx.doi.org/10.1242/dmm.022475 |
| Language: | English |
| Additional information: | Copyright © 2016. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
| Keywords: | EIU, Flow cytometry, OCT |
| 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.ucl.ac.uk/id/eprint/1481081 |
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