September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Expression of VEGF-A, VEGF-C, VEGF-D and soluble receptors in Clinical Age-Related Macular Degeneration
Author Affiliations & Notes
  • Gianna C Teague
    Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States
  • Jie Ma
    Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States
  • Walter Johnson
    Department of Physics, Suffolk University, Boston, Massachusetts, United States
  • Megan E Baldwin
    Circadian Technologies Ltd, Opthea Pty Ltd, South Yarra, Victoria, Australia
  • Kameran Lashkari
    Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Gianna Teague, None; Jie Ma, None; Walter Johnson, None; Megan Baldwin, Ophtea Pty Ltd, Circadian Technologies Ltd (S); Kameran Lashkari, Massachusetts Eye & Ear Infirmary (F)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3698. doi:
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      Gianna C Teague, Jie Ma, Walter Johnson, Megan E Baldwin, Kameran Lashkari; Expression of VEGF-A, VEGF-C, VEGF-D and soluble receptors in Clinical Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3698.

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

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Abstract

Purpose : The significance of the VEGF-A as a key player in angiogenesis and neovascularization is widely known, and has lead to the development of multiple anti-VEGF-A drugs for treatment. Our study highlights the other members in the VEGF/VEGFR family to discover the extent of their involvement in AMD by measuring circulating levels of VEGF-A, VEGF-C, VEGF-D and their soluble (s) cognate receptors in the plasma of subjects with various stages of AMD. Comparison between plasma levels of these growth factors with expression in ocular tissue staged for AMD was evaluated, particularly focusing on neovascular (wet) AMD.

Methods : Human plasma samples were collected from 174 subjects and staged according to the following: Non-AMD Controls, Dry AMD (AREDS Stage I, Stage II, and Stage III), and Neovascular AMD. All samples were analyzed via ELISAs to measure the levels of VEGF-A, VEGF-C, VEGF-D, and their soluble receptors, VEGFR-2 and VEGFR-3. Analysis of plasma data was performed using the Mann-Whitney test. VEGF/VEGFR expression was confirmed using immunohistochemistry (IHC) on human paraffin-embedded ocular tissue staged for AMD.

Results : Analysis by ELISA determined that mean VEGF-C and VEGF-D concentrations were significantly elevated in human plasma; the levels of VEGF-A, -C, and -D were independent of age. Our data showed that VEGF-A, VEGFR-2 and soluble VEGFR-3 levels were not significantly influenced by the stage of AMD. VEGF-C and -D levels showed strong significant shifts in neovascular AMD with Z-Scores of 3.6647 (p = 0.00013) and 1.7859 (p = 0.03673), respectively. Using IHC, VEGF-C, VEGF-D and VEGFR-3 were detected in retinal ganglion cells, nuclear layers, photoreceptors, and RPE in control eyes, and expressed at higher levels in AMD staged eyes. In neovascular AMD, VEGF-C, VEGF-D and VEGFR-3 were expressed in RPE and endothelial cells associated with CNV membranes. These expression patterns were similar to those of VEGF-A and VEGFR-2.

Conclusions : Analysis of the VEGF/VEGFR family in human plasma indicates that VEGF-A is not the only member associated with AMD. Elevated levels of VEGF-C and VEGF-D correlate significantly with neovascular AMD. These findings indicate that these growth factors may be additional targets for treatment of neovascular AMD.

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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