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Christina Nuernberg, Norbert Kociok, Claudia Brockmann, Olaf Strauss, Ria Baumgrass, Timo Lischke, Sandra Beer-Hammer, Antonia M Joussen; VEGF expression in macrophages does not affect hypoxia induced neovascularization. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2307. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Inflammation plays an important role in pathological retinal vascularization: previous studies showed that depletion of macrophages can reduce VEGF levels in the growing retina. We investigated the prevalent hypothesis that VEGF secreted by macrophages and granulocytes affects retinal vascularization.
VEGF fl/fl LysMCre +/- mice, which selectively lack VEGF expression in macrophages and granulocytes, and their respective controls were used for the experiments. To induce angiogenesis in the retina, we implemented the established mouse model of oxygen-induced retinopathy. Investigative time points were chosen to be p14 and p17.<br /> Whole flatmounts of the conditional and control littermate mice retinas were dissected and stained with an endothelial-specific (anti-Isolectin IB4) and an anti-CD11b myeloid-specific cell marker. We imaged the flatmounts to quantify and correlate the proliferation of new vessels both in oxygen-treated mice and their controls kept under normal housing conditions. mRNA levels of VEGF and Cre in the retina and the respective control organs were analyzed by Quantitative Real Time PCR. Quantification of the number of macrophages and granulocytes after oxygen treatment compared to untreated control mice in the retina was assessed by FACS-analysis.
Quantification of the avascular area showed no significant differences between control and VEGF fl/fl LysMCre +/- mice after oxygen exposure. Likewise, there was no significant difference in VEGF or Cre expression in the retina of oxygen-treated control and LysMCre fl/fl Cre +/- mice when compared to the respective control mice kept under housing conditions.<br /> The FACS analysis of the retina showed a significantly higher number of inflammatory cells on p14 compared to p17.
Our data show that VEGF derived from macrophages and granulocytes does not affect the formation of pathological blood vessels in this oxygen-induced retinopathy mouse model. We conclude that VEGF expression by macrophages and granulocytes does not play a significant role in the pathogenesis of oxygen-induced retinopathy. Though macrophages do not contribute to angiogenesis through direct expression of VEGF, they may control the VEGF level in the retina through interactions with other players, e.g. Mueller cells.
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