Deletion of myosin VI causes slow retinal optic neuropathy and age-related macular degeneration (AMD)-relevant retinal phenotype.
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.
Werner Reichardt Centre for Integrative Neuroscience (CIN)/Institute for Ophthalmic Research, University of Tübingen, Otfried-Müller-Str. 25, 72076, Tübingen, Germany. timm.schubert@uni-tuebingen.de.
Timm
T
Schubert
Institute of Anatomy, Department of Clinical Anatomy and Cell Analysis, University of Tübingen, Elfriede-Aulhorn-Str. 8, 72076, Tübingen, Germany. corinna.gleiser@klinikum.uni-tuebingen.de.
Corinna
C
Gleiser
Experimental Vitreoretinal Surgery, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, 72076, Tübingen, Germany. peter.heiduschka@ukmuenster.de.|University Eye Hospital Münster, Westfälische Wilhelms-University of Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany. peter.heiduschka@ukmuenster.de.
Peter
P
Heiduschka
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. ch.franz@gmail.com.
Christoph
C
Franz
Institute of Zoology, Cell and Matrix Biology, Johannes Gutenberg University of Mainz, Johann-Joachim-Becher-Weg 11, 55128, Mainz, Germany. nagelwol@uni-Mainz.de.
Kerstin
K
Nagel-Wolfrum
Cell Death Mechanisms Group, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany. ayse.sahaboglu-tekgoez@klinikum.uni-tuebingen.de.
Ayse
A
Sahaboglu
Molecular Genetics, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany. nicole.weisschuh@uni-tuebingen.de.
Nicole
N
Weisschuh
Werner Reichardt Centre for Integrative Neuroscience (CIN)/Institute for Ophthalmic Research, University of Tübingen, Otfried-Müller-Str. 25, 72076, Tübingen, Germany. gordon.eske@klinikum.uni-tuebingen.de.
Gordon
G
Eske
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. KarinRohbock@yahoo.de.
Karin
K
Rohbock
Cell Death Mechanisms Group, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany. norman.rieger@medizin.uni-tuebingen.de.
Norman
N
Rieger
Cell Death Mechanisms Group, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany. francois.paquet-durand@klinikum.uni-tuebingen.de.
François
F
Paquet-Durand
Molecular Genetics, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany. wissinger@uni-tuebingen.de.
Bernd
B
Wissinger
Institute of Zoology, Cell and Matrix Biology, Johannes Gutenberg University of Mainz, Johann-Joachim-Becher-Weg 11, 55128, Mainz, Germany. wolfrum@uni-mainz.de.
Uwe
U
Wolfrum
Institute of Anatomy, Department of Clinical Anatomy and Cell Analysis, University of Tübingen, Elfriede-Aulhorn-Str. 8, 72076, Tübingen, Germany. bernhard.hirt@klinikum.uni-tuebingen.de.
Bernhard
B
Hirt
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. wibke.singer@uni-tuebingen.de.
Wibke
W
Singer
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. lukas.ruettiger@uni-tuebingen.de.
Lukas
L
Rüttiger
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. ulrike.zimmermann@uni-tuebingen.de.
Ulrike
U
Zimmermann
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. marlies.knipper@uni-tuebingen.de.
Marlies
M
Knipper
D000818:Animals; D017353:Gene Deletion; D005838:Genotype; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009901:Optic Nerve Diseases / Q000235:genetics* / Q000473:pathology; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D012160:Retina / Q000378:metabolism / Q000502:physiology
C089785:myosin VI; D018995:Myosin Heavy Chains
Bipolar cell; Choriocapillaris; Inner retina; Mouse model; Outer retina; Stereocilia; Synapse; Translocator protein TSPO