July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
A Bioactive Small Molecule Derivative of Fluoro-catechol Ester of 3-Hydroxy-Benzoic Acid Inhibits High Glucose/Hypoxia-Induced Endothelial Switch to Angiogenic Phenotype in Diabetes Induced Retinal Microvasculopathy
Author Affiliations & Notes
  • Ahmed S Ibrahim
    Oral Biology and Diagnostic Science, Augusta University, Augusta, GA, Georgia
    Biochemistry, Faculty of Pharmacy, Mansoura University, Egypt
  • Shaimaa Eltanani
    Clinical Pathology, Faculty of Medicine, Mansoura University, Egypt
  • Heba Saleh
    Oral Biology and Diagnostic Science, Augusta University, Augusta, GA, Georgia
  • Ibrahim Eldeeb
    Institute for Glycomics, Griffith University, Queensland, Australia
  • Farid Badria
    Pharmacognosy, Faculty of Pharmacy, Mansoura University, Egypt
  • Mohamed Al-Sayed Al-Shabrawey
    Oral Biology and Diagnostic Science, Augusta University, Augusta, GA, Georgia
  • Footnotes
    Commercial Relationships   Ahmed Ibrahim, None; Shaimaa Eltanani, None; Heba Saleh, None; Ibrahim Eldeeb, None; Farid Badria, None; Mohamed Al-Shabrawey, None
  • Footnotes
    Support  American Heart Association Grant 18CDA34080403
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5709. doi:
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      Ahmed S Ibrahim, Shaimaa Eltanani, Heba Saleh, Ibrahim Eldeeb, Farid Badria, Mohamed Al-Sayed Al-Shabrawey; A Bioactive Small Molecule Derivative of Fluoro-catechol Ester of 3-Hydroxy-Benzoic Acid Inhibits High Glucose/Hypoxia-Induced Endothelial Switch to Angiogenic Phenotype in Diabetes Induced Retinal Microvasculopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5709.

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

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Abstract

Purpose : Diabetes induced retinal microvasculopathy is the most common complication of diabetic retinopathy (DR) that eventually occurs in nearly all patients with diabetes. Anti-VEGF drugs, although proven beneficial, are only effective in nearly 50% of patients, and thus brought the need for alternative or complementary therapies. Aberrant glucose transport and metabolism by retinal endothelial cells are attracting great interest as disease-related mechanisms with little attention in the context of DR.Fluoro-catechol ester of 3-Hydroxy-benzoic acid (FCEHB) has been reported to inhibit glucose transport; nevertheless, its effect on treating vascular abnormalities typical of DR has not been tested so far.

Methods : Human retinal endothelial cells (HRECs) were used and treated with high glucose (HG, 30 mM) or osmotic control with or without hypoxia (1%O2) in presence or absence of (FCEHB, 10 μM) or Vehicle (DMSO). Barrier function was assessed by Electric Cell-substrate Impedance Sensing (ECIS) and immunofluorescence of Zonula Occluden-1 (ZO-1) organization. The angiogenic potential of HRECs was evaluated by migration; sprouting and tube formation. Group differences were evaluated by ANOVA followed by Tukey Posthoc test.

Results : Increased expression of glucose transporter (GLUT1) and its translocation from the cytosol to the plasma membrane have been observed in response to simultaneous insults of HG/ hypoxia. This was associated with (a) an accelerated breakdown of HREC barrier integrity, indicated by the significant drop in transendothelial electric resistance; (b) a marked disruption of ZO-1; (c) a dramatic enhancement of HRECs migration; and (d) an induction of profound HREC neovascularization and tube formation. Importantly, FCEHB was able to remarkably restore the drop in barrier function induced by both HG and hypoxia and to reverse their disruptive effects on ZO-1 integrity. FCEHB was also able to effectively mitigate angiogenic effects of both HG and hypoxia on HRECs, including increased cell migration and tube formation, without affecting cell viability.

Conclusions : To our knowledge, this is the first report that FCEHB has a protective effect against high glucose/hypoxia-Induced retinal microvasculopathy. This finding may lead to new therapeutic approaches for treatment of DR.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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