title: miRNAs 182 and 183 are necessary to maintain adult cone photoreceptor outer segments and visual function.
abstract: The outer segments of cones serve as light detectors for daylight color vision, and their dysfunction leads to human blindness conditions. We show that the cone-specific disruption of DGCR8 in adult mice led to the loss of miRNAs and the loss of outer segments, resulting in photoreceptors with significantly reduced light responses. However, the number of cones remained unchanged. The loss of the outer segments occurred gradually over 1 month, and during this time the genetic signature of cones decreased. Reexpression of the sensory-cell-specific miR-182 and miR-183 prevented outer segment loss. These miRNAs were also necessary and sufficient for the formation of inner segments, connecting cilia and short outer segments, as well as light responses in stem-cell-derived retinal cultures. Our results show that miR-182- and miR-183-regulated pathways are necessary for cone outer segment maintenance in vivo and functional outer segment formation in vitro.
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Volker
authors.initials: V
authors.lastname: Busskamp
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Krol
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; University of Basel, 4058 Basel, Switzerland.
authors.forename: Dasha
authors.initials: D
authors.lastname: Nelidova
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; University of Basel, 4058 Basel, Switzerland.
authors.forename: Janine
authors.initials: J
authors.lastname: Daum
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Tamas
authors.initials: T
authors.lastname: Szikra
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Ben
authors.initials: B
authors.lastname: Tsuda
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Josephine
authors.initials: J
authors.lastname: Jüttner
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Karl
authors.initials: K
authors.lastname: Farrow
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Brigitte Gross
authors.initials: BG
authors.lastname: Scherf
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Claudia Patricia Patino
authors.initials: CP
authors.lastname: Alvarez
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Christel
authors.initials: C
authors.lastname: Genoud
authors.affiliation: Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Department of Ophthalmology, Eberhard-Karls University, 72076 Tübingen, Germany.
authors.forename: Vithiyanjali
authors.initials: V
authors.lastname: Sothilingam
authors.affiliation: Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Department of Ophthalmology, Eberhard-Karls University, 72076 Tübingen, Germany.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tanimoto
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Stadler
authors.affiliation: Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Department of Ophthalmology, Eberhard-Karls University, 72076 Tübingen, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Seeliger
authors.affiliation: Institute for Molecular Health Sciences, ETH, 8093 Zürich.
authors.forename: Markus
authors.initials: M
authors.lastname: Stoffel
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; University of Basel, 4058 Basel, Switzerland. Electronic address: witold.filipowicz@fmi.ch.
authors.forename: Witold
authors.initials: W
authors.lastname: Filipowicz
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland. Electronic address: botond.roska@fmi.ch.
authors.forename: Botond
authors.initials: B
authors.lastname: Roska
mesh_terms: D000375:Aging; D000818:Animals; D055786:Gene Knockout Techniques; D006801:Humans; D008027:Light; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D014785:Vision, Ocular / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C540524:Mirn182 microRNA, mouse; C543802:Mirn183 microRNA, mouse