posted on 2020-04-02, 16:41authored byStefanie M. Hauck, Stephanie Schoeffmann, Barbara Amann, Manfred Stangassinger, Hartmut Gerhards, Marius Ueffing, Cornelia A. Deeg
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.
Keywords: inflammation • blood-retinal barrier • Mueller glia • autoimmune disease • clinical proteomics • uveitis