June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Dicer Loss Leads to Müller Cell Gliosis in the Mouse Retina
Author Affiliations & Notes
  • Vijay Sarthy
    Ophthal-Feinberg Med Sch, Northwestern University, Chicago, IL
  • V. Joseph Dudley
    Ophthal-Feinberg Med Sch, Northwestern University, Chicago, IL
  • Deniz Dalkara
    Chemical and Biomolecular Engineering, The Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA
  • David Schaffer
    Chemical and Biomolecular Engineering, The Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA
  • John Flannery
    Chemical and Biomolecular Engineering, The Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA
  • Footnotes
    Commercial Relationships Vijay Sarthy, None; V. Joseph Dudley, None; Deniz Dalkara, None; David Schaffer, None; John Flannery, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5584. doi:https://doi.org/
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      Vijay Sarthy, V. Joseph Dudley, Deniz Dalkara, David Schaffer, John Flannery; Dicer Loss Leads to Müller Cell Gliosis in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5584. doi: https://doi.org/.

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

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Abstract

Purpose: Dicer1 is an endoribonuclease essential for generating the majority of mature miRNAs, and disruption of the Dicer1 gene results in the loss of virtually all microRNAs. To examine the phenotypic consequences of miRNA loss in retinal glia, we conditionally-knocked out Dicer1 gene in Müller glia in the adult mouse retina.

Methods: Dicer1-floxed mice were intravitreally injected with ShH10-Cre, which was generated by cloning Cre into ShH10, an Adeno-associated virus (AAV) variant (closely related to AAV serotype 6) that selectively infects retinal Müller cells.

Results: In tomato-GFP reporter mice injected with ShH10-Cre, very little GFP expression was seen at seven days following virus injection. By 30days, however, extensive GFP expression was evident only in cells with Müller cell morphology. These data show that ShH10-cre transduces Müller cells at a high efficiency and that Cre expression is maximal at 30 days. In Dicer1-floxed mice intravitreally injected with ShH10-Cre, histological sections showed no obvious changes in retinal morphology, except that Müller cells processes were prominent, a hallmark feature of gliosis. Immunocytochemical studies with anti-GFAP showed that GFAP was strongly expressed in Müller cells in these retinas. No GFAP-immunostaining was seen in control retinas or in retinas 7 days after virus injection. qPCR studies further showed that there was an increase in GFAP and Socs3 transcripts in retinas with virus-injection.

Conclusions: Our studies lead to the surprising finding that conditional inactivation of Dicer1 gene in the adult mouse retina leads to expression of markers of gliosis in Müller cells. These results further suggest that Müller cell gliosis can occur independently of retinal injury or degeneration.

Keywords: 603 Muller cells • 533 gene/expression • 699 retinal glia  
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