Amyloid Precursor-Like Protein 2 deletion-induced retinal synaptopathy related to congenital stationary night blindness: structural, functional and molecular characteristics

Autor: Marc Abitbol, Virginie Dinet, Roberto Cappai, Yvan Arsenijevic, Na An, Francine Behar-Cohen, Mohamed El Sanharawi, Giuseppe D. Ciccotosto, Laurent Jonet, Frédéric Mascarelli, Céline Borras, Michèle Savoldelli, Kimberley Delaunay, Corinne Kostic, Caroline Pirou, Isabelle Ranchon-Cole
Přispěvatelé: BMC, BMC, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Pathology [Melbourne, Australie], University of Melbourne-Bio21 Molecular Science & Biotechnology Institute [Melbourne] (School of Chemistry), Faculty of Science [Melbourne], University of Melbourne-University of Melbourne-Faculty of Science [Melbourne], University of Melbourne, Equipe Biophysique Neurosensorielle [Neuro-Dol], Neuro-Dol (Neuro-Dol), Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unit of Gene Therapy & Stem Cell Biology [Lausanne, Suisse], Université de Lausanne = University of Lausanne (UNIL)-Fondation Asile des aveugles - Hôpital Ophtalmique Jules-Gonin [Lausanne], This work was supported by the National Health and Medical Research Council(NHMRC) to RC., Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UP7) - École pratique des hautes études (EPHE) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Pierre et Marie Curie - Paris 6 (UPMC), Bio21 Institute [Melbourne, Australie], Laboratoire de Biophysique Sensorielle, Université d'Auvergne - Clermont-Ferrand I, Unit of Gene Therapy & Stem Cell Biology, University of Lausanne, Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University of Melbourne-Bio21 Institute [Melbourne, Australie], Neuro-Dol ( Neuro-Dol ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Neuro-Dol - Clermont Auvergne ( Neuro-Dol ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ) -Université Clermont Auvergne ( UCA ), Université de Lausanne - UML [Suisse]-Fondation Asile des aveugles - Hôpital Ophtalmique Jules-Gonin [Lausanne, Suisse], Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Neuro-Dol (Neuro-Dol), Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA), Université de Lausanne (UNIL)-Fondation Asile des aveugles - Hôpital Ophtalmique Jules-Gonin [Lausanne]
Rok vydání: 2016
Předmět:
0301 basic medicine
Retinal degeneration
Aging
genetic structures
Transcription
Genetic
[SDV]Life Sciences [q-bio]
Ribbon synapse
Synaptic Transmission
chemistry.chemical_compound
Amyloid beta-Protein Precursor
Night Blindness
Amyloid precursor protein
Myopia
Congenital stationary night blindness
Mice
Knockout
biology
Cell Differentiation
Eye Diseases
Hereditary
Genetic Diseases
X-Linked
[SDV] Life Sciences [q-bio]
medicine.anatomical_structure
Synaptopathy
Differentiation
Aging/pathology
Amacrine Cells/metabolism
Amyloid beta-Protein Precursor/chemistry
Amyloid beta-Protein Precursor/deficiency
Amyloid beta-Protein Precursor/genetics
Amyloid beta-Protein Precursor/metabolism
Animals
Animals
Newborn
Complement System Proteins/metabolism
Dendrites/metabolism
Eye Diseases
Hereditary/genetics
Eye Diseases
Hereditary/pathology
Eye Diseases
Hereditary/physiopathology
Gene Deletion
Genetic Diseases
X-Linked/genetics
Genetic Diseases
X-Linked/pathology
Genetic Diseases
X-Linked/physiopathology
Mice
Inbred C57BL
Myopia/genetics
Myopia/pathology
Myopia/physiopathology
Neurogenesis
Night Blindness/genetics
Night Blindness/pathology
Night Blindness/physiopathology
Photoreceptor Cells
Vertebrate/metabolism
Photoreceptor Cells
Vertebrate/pathology
Photoreceptor Cells
Vertebrate/ultrastructure
Presynaptic Terminals/metabolism
Presynaptic Terminals/ultrastructure
RNA
Messenger/genetics
RNA
Messenger/metabolism
Retinal Bipolar Cells/metabolism
Retinal Bipolar Cells/pathology
Retinal Bipolar Cells/ultrastructure
Transcription Factors/metabolism
Amyloid precursor-like protein 2
Synapses
Transcription
Photoreceptor Cells
Vertebrate
Retinal Bipolar Cells
Presynaptic Terminals
03 medical and health sciences
Cellular and Molecular Neuroscience
Night vision
medicine
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
RNA
Messenger
Molecular Biology
Retina
[ SDV ] Life Sciences [q-bio]
Research
Retinal
Complement System Proteins
Dendrites
Inner plexiform layer
medicine.disease
030104 developmental biology
Amacrine Cells
chemistry
biology.protein
sense organs
Neuroscience
Transcription Factors
Zdroj: Molecular Brain
Molecular Brain, 2015, 9 (1), pp.64. ⟨10.1186/s13041-016-0245-z⟩
Molecular Brain, BioMed Central, 2016, <10.1186/s13041-016-0245-z>
Molecular Brain, 2015, 9 (1), pp.64. 〈10.1186/s13041-016-0245-z〉
Molecular brain, vol. 9, no. 1, pp. 64
ISSN: 1756-6606
DOI: 10.1186/s13041-016-0245-z⟩
Popis: Background Amyloid precursor protein knockout mice (APP-KO) have impaired differentiation of amacrine and horizontal cells. APP is part of a gene family and its paralogue amyloid precursor-like protein 2 (APLP2) has both shared as well as distinct expression patterns to APP, including in the retina. Given the impact of APP in the retina we investigated how APLP2 expression affected the retina using APLP2 knockout mice (APLP2-KO). Results Using histology, morphometric analysis with noninvasive imaging technique and electron microscopy, we showed that APLP2-KO retina displayed abnormal formation of the outer synaptic layer, accompanied with greatly impaired photoreceptor ribbon synapses in adults. Moreover, APLP2-KO displayed a significant decease in ON-bipolar, rod bipolar and type 2 OFF-cone bipolar cells (36, 21 and 63 %, respectively). Reduction of the number of bipolar cells was accompanied with disrupted dendrites, reduced expression of metabotropic glutamate receptor 6 at the dendritic tips and alteration of axon terminals in the OFF laminae of the inner plexiform layer. In contrast, the APP-KO photoreceptor ribbon synapses and bipolar cells were intact. The APLP2-KO retina displayed numerous phenotypic similarities with the congenital stationary night blindness, a non-progressive retinal degeneration disease characterized by the loss of night vision. The pathological phenotypes in the APLP2-KO mouse correlated to altered transcription of genes involved in pre- and postsynatic structure/function, including CACNA1F, GRM6, TRMP1 and Gα0, and a normal scotopic a-wave electroretinogram amplitude, markedly reduced scotopic electroretinogram b-wave and modestly reduced photopic cone response. This confirmed the impaired function of the photoreceptor ribbon synapses and retinal bipolar cells, as is also observed in congenital stationary night blindness. Since congenital stationary night blindness present at birth, we extended our analysis to retinal differentiation and showed impaired differentiation of different bipolar cell subtypes and an altered temporal sequence of development from OFF to ON laminae in the inner plexiform layer. This was associated with the altered expression patterns of bipolar cell generation and differentiation factors, including MATH3, CHX10, VSX1 and OTX2. Conclusions These findings demonstrate that APLP2 couples retina development and synaptic genes and present the first evidence that APLP2 expression may be linked to synaptic disease. Electronic supplementary material The online version of this article (doi:10.1186/s13041-016-0245-z) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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