September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Elevated homocysteine in the vitreous of diabetic patients and blood of type 1 and 2 diabetic animal models; Potential role of homocysteine in blood retinal barrier dysfunction
Author Affiliations & Notes
  • Isha Sharma
    augusta university, Augusta, Georgia, United States
  • Ahmed S Ibrahim
    augusta university, Augusta, Georgia, United States
  • Heba Mohamed Saleh
    augusta university, Augusta, Georgia, United States
  • Shaikh Rizwan
    augusta university, Augusta, Georgia, United States
  • Gregory Ing Liou
    augusta university, Augusta, Georgia, United States
  • Mohamed Al-Sayed Al-Shabrawey
    augusta university, Augusta, Georgia, United States
  • Amany M Tawfik
    augusta university, Augusta, Georgia, United States
  • Footnotes
    Commercial Relationships   Isha Sharma, None; Ahmed Ibrahim, None; Heba Saleh, None; Shaikh Rizwan, None; Gregory Liou, None; Mohamed Al-Shabrawey, None; Amany Tawfik, None
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3218. doi:
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      Isha Sharma, Ahmed S Ibrahim, Heba Mohamed Saleh, Shaikh Rizwan, Gregory Ing Liou, Mohamed Al-Sayed Al-Shabrawey, Amany M Tawfik; Elevated homocysteine in the vitreous of diabetic patients and blood of type 1 and 2 diabetic animal models; Potential role of homocysteine in blood retinal barrier dysfunction. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3218.

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

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Abstract

Purpose : Homocysteine (Hcy) is a sulfur-containing amino acid which has been reported to be elevated in plasma, vitreous and aqueous of patients with diabetic retinopathy (DR). This study is aiming to investigate the potential role of Hcy in DR via alteration of retinal endothelial cells barrier function and enhancing their angiogenic potential.

Methods : ELISA kit has been used to measure Hcy levels in the vitreous of patients with DR and in the blood of animal models of type 1 diabetes (akita mice and streptozocin injected mice & rats) and in db/db mice as a model of type 2 diabetes. Human retinal endothelial cells (HRECs) treated for 24 hours with and without Hcy (20, 50, 100 µM) were evaluated for blood retinal barrier integrity by FITC–Dextran flux permeability assay, Electric Cell-substrate Impedance Sensing (ECIS) to measure the transelectrical resistance (TER) as well as evaluation of the level and organization of tight junction proteins, ZO-1 and occludin by Western blot and immunofluorescence (IF). Furthermore, angiogenic potential of HRECs was evaluated by tube formation assay.

Results : Hcy was significantly elevated in human patients and in all animal models of diabetes. Hcy incapacitated the barrier function and enhanced angiogenesis in HRECs as evinced by increased leakage in Hcy treated HRECs in FITC-dextran permeability assay, decreased TER, down-regulation of tight junction proteins as well as induction of tube formation in Hcy-treated HRECs.

Conclusions : Our data suggest the involvement of Hcy in the development and/or the progression of DR. Therefore, elimination of excess Hcy might provide a potential therapeutic avenue to prevent microvascular dysfunction associated with DR.

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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