DICER1 is essential for survival of postmitotic rod photoreceptor cells in mice

Thomas R. Sundermeier, Ning Zhang, Frans Vinberg, Debarshi Mustafi, Hideo Kohno, Marcin Golczak, Xiaodong Bai, Akiko Maeda, Vladimir J. Kefalov, Krzysztof Palczewski

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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.

Original languageEnglish
Pages (from-to)3780-3791
Number of pages12
JournalFASEB Journal
Volume28
Issue number8
DOIs
StatePublished - Aug 2014

Keywords

  • Age-related macular degeneration
  • Cell survival
  • Conditional knockout
  • MicroRNA
  • Retina

Fingerprint

Dive into the research topics of 'DICER1 is essential for survival of postmitotic rod photoreceptor cells in mice'. Together they form a unique fingerprint.

Cite this