June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
VEGF-A165b reduces vascular dysfunction in the diabetic retina
Author Affiliations & Notes
  • Nikita Ved
    Genetics, Institute of Ophthalmology, University College London, London, United Kingdom
    Tumour and Vascular Research Laboratories, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom
  • Richard Hulse
    Tumour and Vascular Research Laboratories, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom
  • Samuel Bestall
    Tumour and Vascular Research Laboratories, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom
    School of Life Sciences, Queen's Medical Centre, Nottingham, United Kingdom
  • Lucy Donaldson
    School of Life Sciences, Queen's Medical Centre, Nottingham, United Kingdom
  • James W B Bainbridge
    Genetics, Institute of Ophthalmology, University College London, London, United Kingdom
  • David Bates
    Tumour and Vascular Research Laboratories, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom
  • Footnotes
    Commercial Relationships Nikita Ved, None; Richard Hulse, None; Samuel Bestall, None; Lucy Donaldson, None; James Bainbridge, None; David Bates, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 926. doi:
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    • Get Citation

      Nikita Ved, Richard Hulse, Samuel Bestall, Lucy Donaldson, James W B Bainbridge, David Bates; VEGF-A165b reduces vascular dysfunction in the diabetic retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):926.

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

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Abstract

Purpose: Diabetic macular edema (DME) is associated with an increase in pro-angiogenic VEGF isoforms in the retina, notably VEGF-A165a, resulting in tight-junction degradation and vascular leakage. Anti-angiogenic isoforms, such as VEGF-A165b are down-regulated in the diabetic retina and this may contribute to the vascular dysfunction. The aim of this study is to assess the ability of VEGF-A165b to abrogate blood-retina barrier breakdown and subsequent hyperpermeability.

Methods: Human primary RPE cells were cultured in normal, low glucose (5mM) and high glucose (25mM) media +/- 2.5nM VEGF-A165b and assayed for tight junction integrity through occludin expression and trans-epithelial electrode resistance (TEER). ZO1 and occludin expression and TEER was used to assay RPE tight-junction integrity upon 2.5 nM VEGF-A165a treatment +/- 2.5 nM VEGF165b. In vivo retinal vascular dysfunction was measured in streptozotocin-induced diabetic rats (50mg/kg) after 1 week and 8 weeks of diabetes + / - VEGF-A165b (50ng intravitreally and 20ng/g intraperitoneally biweekly respectively). Evans’ blue extravasation and isolectin B4 staining was used to assess vascular permeability and neovascularisation respectively.

Results: RPE cells cultured in 25mM media showed reduced occludin expression and increased paracellular flux that was restored with VEGF-A165b treatment. VEGF-A165a reduced occludin and ZO1 expression and increased paracellular flux, which were restored by VEGF-A165b. Diabetic rats treated with VEGF-A165b had reduced Evans’ blue extravasation at both 1 (p<0.05) and 8 (p<0.001) weeks post STZ-injection relative to vehicle treated diabetic rats.

Conclusions: VEGF165b is able to restore expression and function of tight junctions upon hyperglycaemic insult and may offer an effective therapeutic approach in treating diabetic macular edema.

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