Label-free LC-MSMS analysis of vitreous from autoimmune uveitis reveals a significant decrease in secreted Wnt signalling inhibitors DKK3 and SFRP2

Equine recurrent uveitis is a severe and frequent blinding disease in horses which presents with auto-reactive invading T-cells, resulting in the destruction of the inner eye. Infiltration of inflammatory cells into the retina and vitreous is driven by currently unknown guidance cues, however surgic...

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Bibliographic Details
Published in:Journal of proteomics 2012-07, Vol.75 (14), p.4545-4554
Main Authors: Hauck, Stefanie M., Hofmaier, Florian, Dietter, Johannes, Swadzba, Margarete E., Blindert, Marcel, Amann, Barbara, Behler, Jennifer, Kremmer, Elisabeth, Ueffing, Marius, Deeg, Cornelia A.
Format: Article
Language:English
Subjects:
Autoimmune disease
coagulation
complement
horses
immunohistochemistry
mass spectrometry
neuroglia
pathogenesis
Protein network analyses
protein synthesis
proteins
proteomics
Retina
Retinal Müller glial cells
Spontaneous animal model
T-lymphocytes
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Summary:Equine recurrent uveitis is a severe and frequent blinding disease in horses which presents with auto-reactive invading T-cells, resulting in the destruction of the inner eye. Infiltration of inflammatory cells into the retina and vitreous is driven by currently unknown guidance cues, however surgical removal of the vitreous (vitrectomy) has proven therapeutically successful. Therefore, proteomic analyses of vitrectomy samples are likely to result in detection of proteins contributing to disease pathogenesis. Vitreous from healthy and ERU diseased horses were directly compared by quantitative mass spectrometry based on label-free quantification of peak intensities across samples. We found a significant upregulation of complement and coagulation cascades and downregulation of negative paracrine regulators of canonical Wnt signalling including the Wnt signalling inhibitors DKK3 and SFRP2. Based on immunohistochemistry, both proteins are expressed in equine retina and suggest localisation to retinal Müller glial cells (RMG), which may be the source cells for these proteins. Furthermore, retinal expression levels and patterns of DKK3 change in response to ERU. Since many other regulated proteins identified here are associated with RMG cells, these cells qualify as the prime responders to autoimmune triggers. This article is part of a Special Issue entitled: “Farm animal proteomics”. [Display omitted] ► Label-free LC-MSMS comparison of vitreous proteins. ► 70 differentially regulated proteins detected in equine recurrent uveitis. ► 28 significantly enriched biological pathways. ► Wnt signalling changes in ERU. ► SFRP2 and Dkk3 link Wnt signalling changes to RMG cells
ISSN:1874-3919
DOI:10.1016/j.jprot.2012.04.052