Hyperhomocysteinemia alters retinal endothelial cells barrier function and angiogenic potential via activation of oxidative stress

Riyaz Mohamed, Isha Sharma, Ahmed Salah Ibrahim, Heba Mohamed Saleh, Nehal M. Elsherbiny, Sadanand T Fulzele, Khaled Elmasry, Sylvia B Smith, Mohamed Al-Shabrawey, Amany Mohamed Tawfik

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Abstract

Hyperhomocysteinemia (HHcy) is associated with several human visual disorders, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Breakdown of the blood-retinal barrier (BRB) is linked to vision loss in DR and AMD. Our previous work revealed that HHcy altered BRB in retinal endothelial cells in vivo. Here we hypothesize that homocysteine (Hcy) alters retinal endothelial cell barrier function and angiogenic potential via activation of oxidative stress. Human retinal endothelial cells (HRECs) treated with and without different concentrations of Hcy showed a reduction of tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance and increased angiogenic potential. In addition, HRECs treated with Hcy showed increased production of reactive oxygen species (ROS). The anti-oxidant N-Acetyl-cysteine (NAC) reduced ROS formation and decreased FITC-dextran leakage in Hcy treated HRECs. A mouse model of HHcy, in which cystathionine-β-synthase is deficient (cbs -/-), was evaluated for oxidative stress by dichlolorofluorescein (DCF), dihydroethidium (DHE) staining. There was a marked increase in ROS production and augmented GSH reductase and antioxidant regulator NRF2 activity, but decreased antioxidant gene expression in retinas of hyperhomocysteinemic mice. Our results suggest activation of oxidative stress as a possible mechanism of HHcy induced retinal endothelial cell dysfunction.

Original languageEnglish (US)
Article number09731
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Hyperhomocysteinemia
Oxidative Stress
Endothelial Cells
Homocysteine
Blood-Retinal Barrier
Reactive Oxygen Species
Macular Degeneration
Diabetic Retinopathy
Antioxidants
Cystathionine
Tight Junction Proteins
Vision Disorders
Electric Impedance
Oxidants
Cysteine
Retina
Oxidoreductases
Staining and Labeling
Gene Expression

ASJC Scopus subject areas

  • General

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Hyperhomocysteinemia alters retinal endothelial cells barrier function and angiogenic potential via activation of oxidative stress. / Mohamed, Riyaz; Sharma, Isha; Ibrahim, Ahmed Salah; Saleh, Heba Mohamed; Elsherbiny, Nehal M.; Fulzele, Sadanand T; Elmasry, Khaled; Smith, Sylvia B; Al-Shabrawey, Mohamed; Tawfik, Amany Mohamed.

In: Scientific Reports, Vol. 7, No. 1, 09731, 01.12.2017.

Research output: Contribution to journalArticle

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