title: GFAP antibodies show protective effect on oxidatively stressed neuroretinal cells via interaction with ERP57.
abstract: The pathogenesis of glaucoma, a common neurodegenerative disease, involves an immunologic component. Changes in the natural autoantibody profile of glaucoma patients were detected, showing not only up-regulated but also down-regulated immunoreactivities. In recent studies we were able to demonstrate that the antibody changes have a large influence on protein profiles of neuroretinal cells. Furthermore we could demonstrate neuroprotective potential of one of the down-regulated antibodies (γ-synuclein antibody). Anti-GFAP antibody is another antibody found down-regulated in glaucoma patients. Since GFAP expression is intensified in glaucomatous retina, the aim of this study was to detect the effect of GFAP antibodies on neuroretinal cells. This is realized with a viability-test as well as proteomic analysis of cells incubated with GFAP antibodies. Furthermore, possible interaction partners of the GFAP antibody in neuroretinal cells were identified by western blot, mass spectrometry and indirect immunofluorescence staining. We found that the GFAP antibody is able to protect cells from oxidative stress, which is due to changed protein expressions of the actin cytoskeleton. Furthermore we detected a cross-reaction of the antibody to endoplasmic reticulum resident protein 57 on the cell membrane, which seems to lead to a changed signaling in the cells triggering the protective effects.
authors.affiliation: Experimental Ophthalmology, Department of Ophthalmology, Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Electronic address: cwilding@eye-research.org.
authors.forename: C
authors.initials: C
authors.lastname: Wilding
authors.affiliation: Experimental Ophthalmology, Department of Ophthalmology, Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Electronic address: kbell@eye-research.org.
authors.forename: K
authors.initials: K
authors.lastname: Bell
authors.affiliation: Experimental Ophthalmology, Department of Ophthalmology, Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Electronic address: sfunke@eye-research.org.
authors.forename: S
authors.initials: S
authors.lastname: Funke
authors.affiliation: Experimental Ophthalmology, Department of Ophthalmology, Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Electronic address: sbeck@eye-research.org.
authors.forename: S
authors.initials: S
authors.lastname: Beck
authors.affiliation: Experimental Ophthalmology, Department of Ophthalmology, Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Electronic address: norbert.pfeiffer@unimedizin-mainz.de.
authors.forename: Norbert
authors.initials: N
authors.lastname: Pfeiffer
authors.affiliation: Experimental Ophthalmology, Department of Ophthalmology, Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Electronic address: grus@eye-research.org.
authors.forename: Franz H
authors.initials: FH
authors.lastname: Grus
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D001323:Autoantibodies / Q000502:physiology*; D015551:Autoimmunity; D002478:Cells, Cultured; D003429:Cross Reactions; D015536:Down-Regulation; D005136:Eye Proteins / Q000378:metabolism; D005901:Glaucoma / Q000235:genetics* / Q000276:immunology*; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology*; D006801:Humans; D018384:Oxidative Stress; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000276:immunology*; D012165:Retinal Ganglion Cells / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D005136:Eye Proteins; D005904:Glial Fibrillary Acidic Protein; C513196:PDIA3 protein, rat; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human
keywords: Autoimmunity; ERP57; GFAP; Glaucoma; Neuroprotection