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Hauck, S.M. ; Schoeffmann, S. ; Amann, B.* ; Stangassinger, M.* ; Gerhards, H.* ; Ueffing, M. ; Deeg , C.A.*

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

J. Proteome Res. 6, 2121-2131 (2007)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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 disease progression and relapses, the molecular processes leading to retinal degeneration and consequent blindness remain unknown. To elucidate such processes, we studied changes in the total retinal proteome of ERU-diseased horses compared to healthy controls. Severe changes in the retinal proteome were found for several markers for blood-retinal barrier breakdown and whose emergence depended upon disease severity. Additionally, uveitic changes in the retina were accompanied by upregulation of 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 Mueller glial cells (RMG) in disease process. To confirm this, we screened for additional RMG-specific markers and could demonstrate that, in uveitic retinas, RMG concomitantly upregulate vimentin and GFAP and downregulate glutamine synthetase. These expression patterns suggest for an activated state of RMG, which further downregulate the expression of pigment epithelium-derived factor (PEDF) and begin expressing interferon-gamma, a pro-inflammatory cytokine typical for T-helper 1 cells. We thus propose that RMG may play a fatal role in uveitic disease progression by directly triggering inflammatory processes through the expression and secretion of interferon-gamma.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter inflammation; blood-retinal barrier; Mueller glia; autoimmune disease; clinical proteomics; uveitis
ISSN (print) / ISBN 1535-3893
e-ISSN 1535-3907
Zeitschrift Journal of Proteome Research
Quellenangaben Band: 6, Heft: 6, Seiten: 2121-2131 Artikelnummer: , Supplement: ,
Verlag American Chemical Society (ACS)
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)