June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
A novel mouse model of neovascular AMD due to Dicer1 deficiency
Author Affiliations & Notes
  • Bradley D Gelfand
    Ophthalmology & Visual Sciences, University of Kentucky, Lexington, KY
  • Charles B Wright
    Ophthalmology & Visual Sciences, University of Kentucky, Lexington, KY
  • Jayakrishna Ambati
    Ophthalmology & Visual Sciences, University of Kentucky, Lexington, KY
  • Footnotes
    Commercial Relationships Bradley Gelfand, None; Charles Wright, None; Jayakrishna Ambati, iVeena (I)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3379. doi:
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      Bradley D Gelfand, Charles B Wright, Jayakrishna Ambati; A novel mouse model of neovascular AMD due to Dicer1 deficiency. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3379.

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

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Purpose: Deficiency of Dicer1, and the resulting accumulation of unprocessed SINE RNAs, is implicated in the pathogenesis of atrophic age-related macular degeneration (AMD), although its role in the neovascular AMD is unknown. We sought to investigate whether human neovascular AMD tissues exhibit evidence of Dicer1 deficiency and whether mouse models of Dicer1 deficiency exhibit pathological ocular neovascularization.

Methods: Postmortem and surgically excised human neovascular AMD specimens were subjected to immunohistochemistry and in situ hybridization to assess Dicer1 and SINE RNA levels. A mouse model of chronic Dicer1 deficiency was investigated for pathological retinal and choroidal neovascularization. Eyes were subjected to histological and biochemical analyses to assess SINE RNA abundance, inflammasome activation, cytokine expression and complement deposition. SINE RNAs were administered to wild-type mice undergoing laser-induced choroidal neovascularization.

Results: Human neovascular AMD tissues exhibit reduced Dicer1 and elevated SINE RNA compared to healthy controls. Dicer1 deficient mice exhibit numerous AMD-related pathologies including spontaneous retinal and choroidal neovascularization, RPE atrophy, SINE RNA accumulation, inflammasome activation, IL-1β expression and complement deposition. SINE RNA administration augments laser induced choroidal neovascularization in wild-type mice.

Conclusions: Recapitulating Dicer1 deficiency observed in human neovascular AMD tissues promotes retinal and choroidal angiogenesis, and several AMD-like features.


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