Retinal Mueller Glial Cells Trigger the Hallmark Inflammatory Process in Autoimmune Uveitis

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• 作者：Stefanie M. Hauck ; Stephanie Schoeffmann ; Barbara Amann ; Manfred Stangassinger ; Hartmut Gerhards ; Marius Ueffing ; Cornelia A. Deeg
• 刊名：Journal of Proteome Research
• 出版年：2007
• 出版时间：June 2007
• 年：2007
• 卷：6
• 期：6
• 页码：2121 - 2131
• 全文大小：738K
• 年卷期：v.6,no.6(June 2007)
• ISSN：1535-3907

文摘

Spontaneous equine recurrent uveitis (ERU) is an incurable autoimmune disease affecting the eye.Although retinal-autoantigen specific T-helper 1 cells have been demonstrated to trigger diseaseprogression and relapses, the molecular processes leading to retinal degeneration and consequentblindness remain unknown. To elucidate such processes, we studied changes in the total retinalproteome of ERU-diseased horses compared to healthy controls. Severe changes in the retinal proteomewere found for several markers for blood-retinal barrier breakdown and whose emergence dependedupon disease severity. Additionally, uveitic changes in the retina were accompanied by upregulationof aldose 1-epimerase, selenium-binding protein 1, alpha crystallin A chain, phosphatase 2A inhibitor(SET), and glial fibrillary acidic protein (GFAP), the latter indicating an involvement of retinal Muellerglial cells (RMG) in disease process. To confirm this, we screened for additional RMG-specific markersand could demonstrate that, in uveitic retinas, RMG concomitantly upregulate vimentin and GFAP anddownregulate glutamine synthetase. These expression patterns suggest for an activated state of RMG,which further downregulate the expression of pigment epithelium-derived factor (PEDF) and beginexpressing interferon-gamma, a pro-inflammatory cytokine typical for T-helper 1 cells. We thus proposethat RMG may play a fatal role in uveitic disease progression by directly triggering inflammatoryprocesses through the expression and secretion of interferon-gamma.