Title: DICER1 is essential for survival of postmitotic rod photoreceptor cells in mice
Abstract: The FASEB JournalVolume 28, Issue 8 p. 3780-3791 Research CommunicationFree to Read DICER1 is essential for survival of postmitotic rod photoreceptor cells in mice Thomas R. Sundermeier, Thomas R. Sundermeier Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USASearch for more papers by this authorNing Zhang, Ning Zhang Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USASearch for more papers by this authorFrans Vinberg, Frans Vinberg Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri, USASearch for more papers by this authorDebarshi Mustafi, Debarshi Mustafi Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USASearch for more papers by this authorHideo Kohno, Hideo Kohno Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USASearch for more papers by this authorMarcin Golczak, Marcin Golczak Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USASearch for more papers by this authorXiaodong Bai, Xiaodong Bai Center for RNA Molecular Biology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USASearch for more papers by this authorAkiko Maeda, Akiko Maeda Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USA Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USASearch for more papers by this authorVladimir J. Kefalov, Vladimir J. Kefalov Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri, USASearch for more papers by this authorKrzysztof Palczewski, Corresponding Author Krzysztof Palczewski [email protected] Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USACorrespondence: Department of Pharmacology, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106-4965, USA. E-mail: [email protected]Search for more papers by this author Thomas R. Sundermeier, Thomas R. Sundermeier Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USASearch for more papers by this authorNing Zhang, Ning Zhang Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USASearch for more papers by this authorFrans Vinberg, Frans Vinberg Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri, USASearch for more papers by this authorDebarshi Mustafi, Debarshi Mustafi Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USASearch for more papers by this authorHideo Kohno, Hideo Kohno Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USASearch for more papers by this authorMarcin Golczak, Marcin Golczak Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USASearch for more papers by this authorXiaodong Bai, Xiaodong Bai Center for RNA Molecular Biology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USASearch for more papers by this authorAkiko Maeda, Akiko Maeda Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USA Department of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USASearch for more papers by this authorVladimir J. Kefalov, Vladimir J. Kefalov Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri, USASearch for more papers by this authorKrzysztof Palczewski, Corresponding Author Krzysztof Palczewski [email protected] Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USACorrespondence: Department of Pharmacology, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106-4965, USA. E-mail: [email protected]Search for more papers by this author First published: 08 May 2014 https://doi.org/10.1096/fj.14-254292Citations: 2 This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Photoreceptor cell death is the proximal cause of blindness in many retinal degenerative disorders; hence, understanding the gene regulatory networks that promote photoreceptor survival is at the forefront of efforts to combat blindness. Down-regulation of the microRNA (miRNA)-processing enzyme DICER1 in the retinal pigmented epithelium has been implicated in geographic atrophy, an advanced form of age-related macular degeneration (AMD). However, little is known about the function of DICER1 in mature rod photoreceptor cells, another retinal cell type that is severely affected in AMD. Using a conditional-knockout (cKO) mouse model, we report that loss of DICER1 in mature postmitotic rods leads to robust retinal degeneration accompanied by loss of visual function. At 14 wk of age, cKO mice exhibit a 90% reduction in photoreceptor nuclei and a 97% reduction in visual chromophore compared with those in control littermates. Before degeneration, cKO mice do not exhibit significant defects in either phototransduction or the visual cycle, suggesting that miRNAs play a primary role in rod photoreceptor survival. Using comparative small RNA sequencing analysis, we identified rod photoreceptor miRNAs of the miR-22, miR-26, miR-30, miR-92, miR-124, and let-7 families as potential factors involved in regulating the survival of rods.—Sundermeier, T. R., Zhang, N., Vinberg, F., Mustafi, D., Kohno, H., Golczak, M., Bai, X., Maeda, A., Kefalov, V. J., Palczewski, K. DICER1 is essential for survival of postmitotic rod photoreceptor cells in mice. FASEB J. 28, 3780–3791 (2014). www.fasebj.org Citing Literature Supporting Information Filename Description fsb2028008044-sup-0001.zipZip archive, 2.8 MB Supplementary material Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume28, Issue8August 2014Pages 3780-3791 RelatedInformation