July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Efavirenz treatment reduces drusen-like lesions and choroidal neovascularization in the retina of 5XFAD mice, an Alzheimer’s disease model
Author Affiliations & Notes
  • Irina A Pikuleva
    Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, United States
  • Aicha Saadane
    Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, United States
  • Nicole El-Darzi
    Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, United States
  • Natalia Mast
    Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, United States
  • George Trichonas
    Ophthalmology and Visual Sciences, University Hospitals, Cleveland, Ohio, United States
    Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, United States
  • Footnotes
    Commercial Relationships   Irina Pikuleva, None; Aicha Saadane, None; Nicole El-Darzi, None; Natalia Mast, None; George Trichonas, None
  • Footnotes
    Support  GM062882, EY018383
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 224. doi:
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      Irina A Pikuleva, Aicha Saadane, Nicole El-Darzi, Natalia Mast, George Trichonas; Efavirenz treatment reduces drusen-like lesions and choroidal neovascularization in the retina of 5XFAD mice, an Alzheimer’s disease model
      . Invest. Ophthalmol. Vis. Sci. 2018;59(9):224.

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

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Abstract

Purpose : To conduct retinal characterization of 9-month old 5XFAD mice, untreated (Utx) and treated (Tx) for 8 months with a small dose (0.1 mg/day/kg of body weight) of efavirenz, the anti-HIV drug. Previously, we conducted brain evaluations of efavirenz Utx and Tx mice and found that efavirenz administration enhanced cholesterol turnover in the 5XFAD brain and significantly ameliorated the manifestations of Alzheimer’s disease.

Methods : Mouse retinas were evaluated by high resolution spectral domain optical coherence tomography, fluorescein/indocyanine green angiography and immuno/histochemistry. Retinal sterols were quantified by gas chromatography-mass spectrometry.

Results : About 70% of Utx and 40% of Tx 5XFAD mice had drusen-like lesions as well as disturbed retinal layers on spectral domain optical coherence tomography. Also, about 40% of Utx and 7% of Tx 5XFAD had choroidal neovascularization as assessed by fluorescein/indocyanine green angiography. The investigation of the content of the drusen-like deposits revealed the presence of amyloid dense-core plaques, activated microglial cells, and cholesterol. The affected area had intensive vimentin immunoreactivity attributable to fibroblasts. Stainings for endothelial cells and vascular endothelial growth factor are in progress. Efavirenz Tx mice had the same content of retinal cholesterol but increased levels of the cholesterol metabolite 24-hydroxycholesterol and cholesterol precursor lathosterol. Retinal sterol quantifications suggested that efavirenz treatment enhanced retinal cholesterol turnover.

Conclusions : 5XFAD mice demonstrate features of wet and dry age-related macular degeneration, which are ameliorated by efavirenz treatment. Mechanistic hypothesis is developed explaining the data obtained and suggesting a possible mechanism for retinal and choroidal abnormalities. 5XFAD mice should be further be investigated as a model for age-related macular degeneration and efavirenz as a potential treatment for this disease.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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