caa a22 4500 606175156 CHVBK 20210128100741.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00018-015-1913-3 doi (NATIONALLICENCE)springer-10.1007/s00018-015-1913-3 Deletion of myosin VI causes slow retinal optic neuropathy and age-related macular degeneration (AMD)-relevant retinal phenotype [Elektronische Daten] [Timm Schubert, Corinna Gleiser, Peter Heiduschka, Christoph Franz, Kerstin Nagel-Wolfrum, Ayse Sahaboglu, Nicole Weisschuh, Gordon Eske, Karin Rohbock, Norman Rieger, François Paquet-Durand, Bernd Wissinger, Uwe Wolfrum, Bernhard Hirt, Wibke Singer, Lukas Rüttiger, Ulrike Zimmermann, Marlies Knipper] The unconventional myosin VI, a member of the actin-based motor protein family of myosins, is expressed in the retina. Its deletion was previously shown to reduce amplitudes of the a- and b-waves of the electroretinogram. Analyzing wild-type and myosin VI-deficient Snell's Waltzer mice in more detail, the expression pattern of myosin VI in retinal pigment epithelium, outer limiting membrane, and outer plexiform layer could be linked with differential progressing ocular deficits. These encompassed reduced a-waves and b-waves and disturbed oscillatory potentials in the electroretinogram, photoreceptor cell death, retinal microglia infiltration, and formation of basal laminar deposits. A phenotype comprising features of glaucoma (neurodegeneration) and age-related macular degeneration could thus be uncovered that suggests dysfunction of myosin VI and its variable cargo adaptor proteins for membrane sorting and autophagy, as possible candidate mediators for both disease forms. The Author(s), 2015 Bipolar cell nationallicence Inner retina nationallicence Outer retina nationallicence Synapse nationallicence Stereocilia nationallicence Translocator protein TSPO nationallicence Choriocapillaris nationallicence Mouse model nationallicence AMD : Age-related macular degeneration nationallicence AP-2 : Adaptor protein 2 nationallicence BI : Basal invaginations nationallicence BM : Bruch's membrane nationallicence CC : Choriocapillaris nationallicence CCDKO : Ccl2/Cx3cr1 double knockout mouse line nationallicence Endo : Endothelial cells nationallicence ERG : Electroretinogram nationallicence GCL : Ganglion cell layer nationallicence INL : Inner nuclear layer nationallicence IOP : Intraocular pressure nationallicence IPL : Inner plexiform layer nationallicence MV : Microvilli nationallicence OLM : Outer limiting membrane nationallicence ONL : Outer nuclear layer nationallicence OP : Oscillatory potentials nationallicence OPL : Outer plexiform layer nationallicence OS : Outer segment nationallicence PKCα : Protein kinase C α nationallicence RBC : Red blood cells nationallicence ROI : Region of interest nationallicence RPE : Retinal pigment epithelium nationallicence +/sv : Heterozygous Snell's Waltzer myosin VI-deficient mouse line nationallicence sv/sv : Homozygous Snell's Waltzer myosin VI-deficient mouse line nationallicence TEM : Transmission electron microscopy nationallicence TUNEL : Terminal deoxynucleotidyltransferase (TdT) dUTP nick end labeling nationallicence VGLUT1 : Vesicular glutamate transporter 1 nationallicence Schubert Timm Werner Reichardt Centre for Integrative Neuroscience (CIN)/Institute for Ophthalmic Research, University of Tübingen, Otfried-Müller-Str. 25, 72076, Tübingen, Germany aut Gleiser Corinna Institute of Anatomy, Department of Clinical Anatomy and Cell Analysis, University of Tübingen, Elfriede-Aulhorn-Str. 8, 72076, Tübingen, Germany aut Heiduschka Peter Experimental Vitreoretinal Surgery, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, 72076, Tübingen, Germany aut Franz Christoph Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany aut Nagel-Wolfrum Kerstin Institute of Zoology, Cell and Matrix Biology, Johannes Gutenberg University of Mainz, Johann-Joachim-Becher-Weg 11, 55128, Mainz, Germany aut Sahaboglu Ayse Cell Death Mechanisms Group, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany aut Weisschuh Nicole Molecular Genetics, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany aut Eske Gordon Werner Reichardt Centre for Integrative Neuroscience (CIN)/Institute for Ophthalmic Research, University of Tübingen, Otfried-Müller-Str. 25, 72076, Tübingen, Germany aut Rohbock Karin Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany aut Rieger Norman Cell Death Mechanisms Group, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany aut Paquet-Durand François Cell Death Mechanisms Group, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany aut Wissinger Bernd Molecular Genetics, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany aut Wolfrum Uwe Institute of Zoology, Cell and Matrix Biology, Johannes Gutenberg University of Mainz, Johann-Joachim-Becher-Weg 11, 55128, Mainz, Germany aut Hirt Bernhard Institute of Anatomy, Department of Clinical Anatomy and Cell Analysis, University of Tübingen, Elfriede-Aulhorn-Str. 8, 72076, Tübingen, Germany aut Singer Wibke Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany aut Rüttiger Lukas Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany aut Zimmermann Ulrike Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany aut Knipper Marlies Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany aut Cellular and Molecular Life Sciences Springer Basel 72/20(2015-10-01), 3953-3969 1420-682X 72:20<3953 2015 72 18 https://doi.org/10.1007/s00018-015-1913-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1913-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Schubert Timm Werner Reichardt Centre for Integrative Neuroscience (CIN)/Institute for Ophthalmic Research, University of Tübingen, Otfried-Müller-Str. 25, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Gleiser Corinna Institute of Anatomy, Department of Clinical Anatomy and Cell Analysis, University of Tübingen, Elfriede-Aulhorn-Str. 8, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Heiduschka Peter Experimental Vitreoretinal Surgery, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Franz Christoph Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Nagel-Wolfrum Kerstin Institute of Zoology, Cell and Matrix Biology, Johannes Gutenberg University of Mainz, Johann-Joachim-Becher-Weg 11, 55128, Mainz, Germany aut NATIONALLICENCE 700 1- Sahaboglu Ayse Cell Death Mechanisms Group, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Weisschuh Nicole Molecular Genetics, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Eske Gordon Werner Reichardt Centre for Integrative Neuroscience (CIN)/Institute for Ophthalmic Research, University of Tübingen, Otfried-Müller-Str. 25, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Rohbock Karin Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Rieger Norman Cell Death Mechanisms Group, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Paquet-Durand François Cell Death Mechanisms Group, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Wissinger Bernd Molecular Genetics, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Wolfrum Uwe Institute of Zoology, Cell and Matrix Biology, Johannes Gutenberg University of Mainz, Johann-Joachim-Becher-Weg 11, 55128, Mainz, Germany aut NATIONALLICENCE 700 1- Hirt Bernhard Institute of Anatomy, Department of Clinical Anatomy and Cell Analysis, University of Tübingen, Elfriede-Aulhorn-Str. 8, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Singer Wibke Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Rüttiger Lukas Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Zimmermann Ulrike Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Knipper Marlies Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/20(2015-10-01), 3953-3969 1420-682X 72:20<3953 2015 72 18