September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Hyperhomocysteinemia Disrupts Retinal Pigment Epithelial Structure and Function with Features of Age-Related Macular Degeneration
Author Affiliations & Notes
  • Amany M Tawfik
    Georgia Regent Univ (GRU), Augusta, Georgia, United States
  • Ahmed S Ibrahim
    Georgia Regent Univ (GRU), Augusta, Georgia, United States
  • Nehal Elsherbini
    Georgia Regent Univ (GRU), Augusta, Georgia, United States
  • Sylvia B Smith
    Georgia Regent Univ (GRU), Augusta, Georgia, United States
  • Mohamed Al-Sayed Al-Shabrawey
    Georgia Regent Univ (GRU), Augusta, Georgia, United States
  • Footnotes
    Commercial Relationships   Amany Tawfik, None; Ahmed Ibrahim, None; Nehal Elsherbini, None; Sylvia Smith, None; Mohamed Al-Shabrawey, None
  • Footnotes
    Support  Startup fund from Georgia Regent University
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Amany M Tawfik, Ahmed S Ibrahim, Nehal Elsherbini, Sylvia B Smith, Mohamed Al-Sayed Al-Shabrawey; Hyperhomocysteinemia Disrupts Retinal Pigment Epithelial Structure and Function with Features of Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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

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Abstract

Purpose : Homocysteine (Hcy) is a risk factor for neurodegenerative and cardiovascular diseases and has been reported to be elevated in patients with age-related macular degeneration (AMD). The current study is aiming to investigate the role of Hcy in development and progression of AMD.

Methods : living mice with elevated levels of Hcy (HHcy) due to lack of the enzyme cystathionine-β-synthase (cbs+/-) and wild type (C57Bl6) mice injected with Hcy intravitrealy were subjected to optical coherence tomography (OCT) and fluorescein angiography (FA). Retinas were harvested for Western Blotting (WB) to detect albumin leakage. Frozen sections were subjected to immunofluorescence (IF) to detect choroidal neovascularization (CNV) using vascular marker isolectinB-4 and some retinas were flatmounted then subjected to IF to detect blood-retinal barrier integrity (anti-ZO-1, anti-occludin) and senescence marker (beta-galactosidase).

Results : OCT evaluation of the retina in cbs+/- mice (24weeks) as well as the Hcy injected mice eyes (8 weeks) revealed features of AMD such as; decreased retinal thickness, subretinal fluid, hyporeflective subretinal lucency, thickened basal laminar membrane, separation of RPE, and increased thickness in the area of the choroid suggesting a possible CNV. Furthermore, OCT examination of middle aged cbs+/- mice (64week) revealed an OCT reminiscent of geographic atrophy/dry AMD with a marked reduction in retina thickness and focal hyper- reflective spots, suggestive migration of RPE and/or inflammatory cell infiltrate. The FA obtained from the cbs+/- mice confirmed the OCT data which revealed a fundus with apparent geographic atrophy and diffuse retinal hyper fluorescence suggestive of RPE atrophy. Furthermore, the FA from the Hcy-injected mice eyes showed diffuse hyper-fluorescence and leakage suggestive of CNV which were confirmed by immunostaining with vascular marker. Fluorescein leakage was confirmed by measuring the albumin leakage into the retina by WB. This was accompanied by a decreased expression of ZO-1 and occludin and up-regulation of beta-galactosidase in the RPE flatmounts of the cbs+/- mice.

Conclusions : The current study is showing strong evidence that HHcy induces retinal phenotype of AMD suggesting that elimination of excess Homocysteine is a potential therapeutic intervention in AMD.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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