Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model
| Autor: | Chu, Colin J., Gardner, Peter J., Copland, David A., Liyanage, Sidath E., Gonzalez-Cordero, Anai, kleine Holthaus, Sophia-Martha, Luhmann, Ulrich F. O., Smith, Alexander J., Ali, Robin R., Dick, Andrew D. |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Neutrophils
Receptors CCR2 lcsh:Medicine Cell Count Eye Severity of Illness Index Uveitis lcsh:Pathology Animals Resource Article Flow cytometry Chemokine CCL2 Inflammation lcsh:R EIU eye diseases Endotoxins Mice Inbred C57BL Disease Models Animal Neutrophil Infiltration OCT Cytokines Female sense organs Tomography Optical Coherence lcsh:RB1-214 |
| Zdroj: | Chu, C J, Gardner, P J, Copland, D A, Liyanage, S E, Gonzalez-Cordero, A, Kleine Holthaus, S-M, Luhmann, U F O, Smith, A J, Ali, R R & Dick, A D 2016, ' Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model ', Disease Models and Mechanisms, vol. 9, no. 4, pp. 473-81 . https://doi.org/10.1242/dmm.022475 Disease Models & Mechanisms, Vol 9, Iss 4, Pp 473-481 (2016) Disease Models & Mechanisms |
| DOI: | 10.1242/dmm.022475 |
| Popis: | 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 either Ccl2 or Ccr2. Optical coherence tomography (OCT) was used for the first time in this model to allow in vivo imaging 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. Summary: A refined platform approach for endotoxin-induced uveitis, using multimodal ex vivo and in vivo assessment, to improve quantification and phenotyping in this ocular model of compartmentalised tissue inflammation. |
| Databáze: | OpenAIRE |
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