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

FASEB J. 2014 Aug;28(8):3780-91. doi: 10.1096/fj.14-254292. Epub 2014 May 8.


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.

Keywords: age-related macular degeneration.; cell survival; conditional knockout; microRNA; retina.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Animals
  • Cell Cycle
  • Cell Survival
  • DEAD-box RNA Helicases / deficiency
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / physiology*
  • Electroretinography
  • Eye Proteins / biosynthesis
  • Eye Proteins / genetics
  • Gene Expression Profiling
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Patch-Clamp Techniques
  • Retinal Degeneration / etiology*
  • Retinal Degeneration / genetics
  • Retinal Degeneration / pathology
  • Retinal Rod Photoreceptor Cells / metabolism
  • Retinal Rod Photoreceptor Cells / pathology*
  • Ribonuclease III / deficiency
  • Ribonuclease III / genetics
  • Ribonuclease III / physiology*
  • Sequence Analysis, RNA
  • Tomography, Optical Coherence
  • Vision, Ocular


  • Eye Proteins
  • MicroRNAs
  • Dicer1 protein, mouse
  • Ribonuclease III
  • DEAD-box RNA Helicases