title: Intravitreal injection of β-crystallin B2 improves retinal ganglion cell survival in an experimental animal model of glaucoma.
abstract: Purpose of this study was to investigate firstly specific proteomic changes within the retina in the course of an animal glaucoma model and to identify secondly new approaches for neuroprotective, therapeutic options in glaucoma by addressing those specific changes. Intraocular pressure was elevated through cauterization of episcleral veins in adult Sprague Dawley rats. Molecular and morphological changes were surveyed using mass spectrometry, optical coherence tomography as well as immunohistochemical cross section- and flat mount stainings. By quantifying more than 1500 retinal proteins, it was found that the HspB5 protein and numerous beta-crystallins showed a uniform and unique shifting expression pattern as a result of different periods of elevated IOP exposure. Crystallins showed a significant downregulation (p<0.05) after 3 weeks of elevated IOP and an upregulation after 7 weeks. Counteracting those typical changes, an intravitreal injection of β-crystallin B2 at the time of IOP elevation was found to reduce retinal ganglion cell loss (p<0.05), decrease of the retinal nerve fiber layer (p<0.05) and impairment of the optic nerve. Ultimately, proteomic data revealed that β-crystallin B2 might influence calcium-depended cell signaling pathways with severe effect on apoptosis and gene regulation. In this context especially annexin A5, calcium-transporting ATPase 1 and various histone proteins seem to play a major role.
authors.affiliation: Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Anders
authors.affiliation: Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Teister
authors.affiliation: Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Aiwei
authors.initials: A
authors.lastname: Liu
authors.affiliation: Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Funke
authors.affiliation: Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Franz H
authors.initials: FH
authors.lastname: Grus
authors.affiliation: Institute for Experimental Ophthalmology, School of Medicine, Westfalian-Wilhelms-University Münster, Münster, Germany.
authors.forename: Solon
authors.initials: S
authors.lastname: Thanos
authors.affiliation: Institute of Neuropathology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Harald D
authors.initials: HD
authors.lastname: von Pein
authors.affiliation: Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Pfeiffer
authors.affiliation: Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Prokosch
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005901:Glaucoma / Q000473:pathology* / Q000503:physiopathology; D007429:Intraocular Pressure; D058449:Intravitreal Injections; D008297:Male; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D038206:beta-Crystallin B Chain / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D038206:beta-Crystallin B Chain; C113634:beta-crystallin B2