June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Dicer is required for survival of mature rod photoreceptors
Author Affiliations & Notes
  • Thomas Sundermeier
    Pharmacology, Case Western Reserve University, Cleveland, OH
  • Ning Zhang
    Pharmacology, Case Western Reserve University, Cleveland, OH
  • Debarshi Mustafi
    Pharmacology, Case Western Reserve University, Cleveland, OH
  • Hideo Kohno
    Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH
  • Krzysztof Palczewski
    Pharmacology, Case Western Reserve University, Cleveland, OH
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 6113. doi:
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      Thomas Sundermeier, Ning Zhang, Debarshi Mustafi, Hideo Kohno, Krzysztof Palczewski; Dicer is required for survival of mature rod photoreceptors. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6113.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: It is impossible to overstate the ubiquity of miRNA-mediated gene regulation in the biology of plants and animals. miRNAs have been implicated in virtually every physiological process and disease pathology in which they have been studied. Despite this widespread functional relevance, surprisingly little is known about the physiological impact of miRNAs in the retina. Inactivation of the miRNA processing enzyme, Dicer, in the developing retina leads to defects in cell fate determination and survival of progenitors, as well as progressive retinal degeneration. However, it’s unclear which retinal cell types require miRNA gene regulation for survival and function or whether miRNAs are required for survival or function of the mature retina. The aim of this study is to address the impact of loss of miRNA gene regulation in mature rod photoreceptors.

Methods: To address these questions we have developed a rod-specific conditional Dicer knockout mouse model. We have analyzed the morphology of mutant mice using light microscopy, immunohistochemistry, and electron microscopy. We are also analyzing the function of the visual system using electroretinogram, single cell electrophysiological approaches, and retinoid analysis.

Results: These animals develop progressive retinal degeneration, beginning with disorganization of rod outer segments around and culminating with degeneration of nearly all photoreceptors. ERG analysis shows progressive loss of rod function, followed by loss of cone-driven visual responses. Electrophysiological and high resolution imaging studies are underway to gain insight into the mechanism of photoreceptor death in these mice.

Conclusions: The observed retinal degeneration demonstrates that miRNAs are essential for the survival and function of mature rod photoreceptors. In addition, these results suggest that miRNAs other than the photoreceptor specific miR-183/96/182 cluster are essential for rod survival and vision.

Keywords: 695 retinal degenerations: cell biology • 533 gene/expression • 539 genetics  
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