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Gianna C Teague, Walter Johnson, Marie Shatos, Megan E Baldwin, Kameran Lashkari; Plasma Levels of VEGF-C and Soluble VEGF Receptor-3 are Elevated in Neovascular AMD. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2327.
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VEGF-A is a key player in angiogenesis associated with wet AMD and has led to development of several anti-VEGF-a drugs for treatment. Our study highlights other VEGF members and their receptors, by measuring circulating levels of VEGF-A, VEGF-C, VEGF-D and their soluble cognate receptors in plasma of subjects with various stages of AMD and their expression in ocular tissue.
Human plasma levels from 174 subjects with AMD or control were subjected to ELISA for levels of VEGF-A, VEGF-C, VEGF-D, sVEGR-2 and sVEGFR-3. Study groups included intermediate stage dry AMD, geographic atrophy, new-onset wet AMD, inactive wet AMD (treated with anti-VEGF therapy) and control. Data were analyzed by both non-parametric (Wilcoxon rank test) and parametric (MANCOVA and Benjamin-Hochberg correction) tests. Tissue expression of these factors was examined by immunohistochemistry of postmortem eyes with neovascular AMD.
VEGF-C plasma levels were significantly elevated in both new-onset untreated wet AMD (p<0.001) and treated inactive wet AMD (p<0.007) using the Wilcoxon test. sVEGFR-3 levels were also significantly elevated in new-onset wet AMD (p<0.001), but returned to baseline levels in treated, inactive wet AMD (p<0.551). MANOVA showed VEGF-C and sVEGFR-3 were significantly elevated for wet and inactive wet AMD as compared to controls. VEGF-C was significantly shifted (p=0.0079), while sVEGFR-3 was shifted at a lower confidence (p=0.098). Both methods of analysis showed that VEGF-A, VEGF-D, and sVEGFR-2 levels were not elevated in the AMD groups. VEGF-A, VEGF-C, sVEGFR-2, and sVEGFR-3 showed no difference among sexes and age groups. VEGF-D had a narrow spread for males, and a wide spread towards high concentration values for females. In post-mortem eyes with neovascular AMD, VEGF-C and VEGFR-3 were observed in the RPE and endothelial cells associated with neovascular membranes.
Analysis of the VEGF/VEGFR family in human plasma indicates that the other growth factors besides VEGF-A may also participate in wet AMD development. Parametric and non-parametric analyses indicate that plasma VEGF-C and sVEGFR-3 levels are correlated with new onset of wet AMD. Additionally, sVEGFR-3 levels appear to normalize with anti-VEGF treatment. These findings indicate that these factors may be used as biomarkers of neovascular AMD.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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