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

Disease Models & Mechanisms
Colin J ChuAndrew D Dick

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 correlate...Continue Reading

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Citations

Nov 4, 2016·International Journal of Molecular Sciences·Inge Van HoveLieve Moons
Jan 24, 2017·Scientific Reports·Peter J GardnerJames W Bainbridge
Aug 21, 2019·Ocular Immunology and Inflammation·Haihan JiaoHolly R Chinnery
Jul 20, 2017·Journal of Neuroinflammation·Deborah A LipskiFrançois Willermain
May 31, 2018·Investigative Ophthalmology & Visual Science·Kathryn L PeppleRussell N Van Gelder
Oct 3, 2018·Clinical & Experimental Optometry : Journal of the Australian Optometrical Association·Haihan JiaoHolly R Chinnery
May 20, 2020·The British Journal of Ophthalmology·Ester CarreñoNicolas Alejandre
Jan 16, 2020·International Journal of Molecular Sciences·Jihae ParkJae Chan Kim
Feb 12, 2021·Science Translational Medicine·Ying Kai ChanGeorge M Church
Feb 26, 2021·Investigative Ophthalmology & Visual Science·Gayathri TummalaKathryn L Pepple
May 19, 2021·Translational Vision Science & Technology·Chulbul M AhmedAlfred S Lewin
Jul 6, 2021·Frontiers in Immunology·Lydia J BradleyLindsay B Nicholson

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Methods Mentioned

BETA
imaging technique
flow
PCR
protein assay
flow cytometry
dissection
profilers
profiler
mechanical dissociation
ELISA

Software Mentioned

ImageJ

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