Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration

Ahmed Salah Ibrahim, Suchreet Mander, Khaled A. Hussein, Nehal M. Elsherbiny, Sylvia B Smith, Mohamed Al-Shabrawey, Amany Mohamed Tawfik

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The disruption of retinal pigment epithelial (RPE) function and the degeneration of photoreceptors are cardinal features of age related macular degeneration (AMD); however there are still gaps in our understanding of underlying biological processes. Excess homocysteine (Hcy) has been reported to be elevated in plasma of patients with AMD. This study aimed to evaluate the direct effect of hyperhomocysteinemia (HHcy) on structure and function of RPE. Initial studies in a mouse model of HHcy, in which cystathionine-β-synthase (cbs) was deficient, revealed abnormal RPE cell morphology with features similar to that of AMD upon optical coherence tomography (OCT), fluorescein angiography (FA), histological, and electron microscopic examinations. These features include atrophy, vacuolization, hypopigmentation, thickened basal laminar membrane, hyporeflective lucency, choroidal neovascularization (CNV), and disturbed RPE-photoreceptor relationship. Furthermore, intravitreal injection of Hcy per se in normal wild type (WT) mice resulted in diffuse hyper-fluorescence, albumin leakage, and CNV in the area of RPE. In vitro experiments on ARPE-19 showed that Hcy dose-dependently reduced tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance, and impaired phagocytic activity. Collectively, our results demonstrated unreported effects of excess Hcy levels on RPE structure and function that lead to the development of AMD-like features.

Original languageEnglish (US)
Pages (from-to)8532-8545
Number of pages14
JournalOncotarget
Volume7
Issue number8
DOIs
StatePublished - Jan 1 2016

Fingerprint

Hyperhomocysteinemia
Retinal Pigments
Macular Degeneration
Homocysteine
Choroidal Neovascularization
Cystathionine
Hypopigmentation
Tight Junction Proteins
Biological Phenomena
Intravitreal Injections
Fluorescein Angiography
Optical Coherence Tomography
Electric Impedance
Atrophy
Albumins
Fluorescence
Epithelial Cells
Electrons
Membranes

Keywords

  • Age related macular degeneration
  • Cystathionine-β-synthase and mouse
  • Gerotarget
  • Hyperhomocysteinemia
  • Retinal pigment epithelium

ASJC Scopus subject areas

  • Oncology

Cite this

Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration. / Ibrahim, Ahmed Salah; Mander, Suchreet; Hussein, Khaled A.; Elsherbiny, Nehal M.; Smith, Sylvia B; Al-Shabrawey, Mohamed; Tawfik, Amany Mohamed.

In: Oncotarget, Vol. 7, No. 8, 01.01.2016, p. 8532-8545.

Research output: Contribution to journalArticle

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