March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Dicer Dysregulation, Alu Rna Accumulation And Inflammasome Activation In Human Ga Eye
Author Affiliations & Notes
  • Sami Dridi
    Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky
  • Valeria Tarallo
    Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky
  • Bradley Gelfand
    Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky
  • Fowler Benjamin
    Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky
  • Jayakrishna Ambati
    Ophthalmology & Visual Sciences, University of Kentucky, Lexington, Kentucky
  • Footnotes
    Commercial Relationships  Sami Dridi, University of Kentucky (P); Valeria Tarallo, University of Kentucky (P); Bradley Gelfand, University of Kentucky (P); Fowler Benjamin, University of Kentucky (P); Jayakrishna Ambati, iVeena-E (P), University of Kentucky (P)
  • Footnotes
    Support  NIH/NEI, Doris Duke Charitable Foundation, Burroughs Wellcome Fund, RPB
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1606. doi:https://doi.org/
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      Sami Dridi, Valeria Tarallo, Bradley Gelfand, Fowler Benjamin, Jayakrishna Ambati; Dicer Dysregulation, Alu Rna Accumulation And Inflammasome Activation In Human Ga Eye. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1606. doi: https://doi.org/.

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

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Abstract
 
Purpose:
 

Geographic atrophy (GA) is an important cause of vision loss in AMD. We have previously shown that Dicer1 dysregulation induced Alu RNA accumulation and thereby led to RPE cell degeneration. Here, we sought to determine the downstream signaling pathways that might be involved.

 
Methods:
 

In an unbiased fashion, we isolated, amplified, and cloned dsRNA species from dsRNA-enriched preparations of RPE of normal and GA human donor eyes. We quantified RNA abundance of Dicer1, Alu, inflammasome components (NLRP3, PYCARD, Caspase-1, IL-18, IL-1β) by QPCR in age-matched normal and diseased human eyes. We also measured protein levels and immunolocalization of theses markers.

 
Results:
 

As previously reported (Kaneko et al., 2011), Dicer1 mRNA and protein levels were significantly decreased in RPE GA compared to normal eyes. Alu RNA and NLRP3 mRNA abundance were dramatically increased in the RPE of human eyes with GA compared to control eyes. Immunostaining and immunolocalization studies showed that the expression of NLRP3, PYCARD and Caspase-1 proteins were also increased. There was also a significant increase in IL-18 mRNA levels and phosphorylation of IRAK1/4 in GA eyes indicative of MyD88 signal transduction.

 
Conclusions:
 

Collectively, our data revealed a role of Dicer1 dysregulation, Alu RNA accumulation and NLRP3 inflammasome activation in GA disease.

 
Keywords: age-related macular degeneration • inflammation • gene/expression 
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