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A. Scott, M. Fruttiger; The Role of VEGF Signalling in Hypoxia-Induced Macrophage Response. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3448.
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Macrophages modulate the vascular response in the oxygen-induced retinopathy model (OIR) in mice. It is possible that this involves signalling via VEGF because macrophages express the VEGF receptor flt-1. This study was performed to determine the CD45-positive macrophage and vascular response in mutant mice containing an inactive Flt-1 tyrosine kinase domain (Flt-1TK - / - mice).
Flt-1TK - / - mice and wild type mice were exposed to 75% oxygen from postnatal day 7 (P7) to P12 and then allowed to recover in room air. They were sacrificed at P15 and retinal wholemounts were examined by immunostaining with CD45. Lectin and EF5 stains allowed coordinate visualisation of retinal vessels and areas of hypoxia.
There was a marked increase of CD45 positive macrophages in hypoxic areas, denoted by the EF5 stain, compared to normoxic areas in both, Flt-1TK - / - mice and controls. The vascular response was similar in mutant and wild type mice.
This suggests that hypoxia induces CD45 positive macrophages to accumulate in avascular areas of the retina but VEGF is an unlikely candidate to mediate this. Nevertheless, the localisation of macrophages adjacent to neovascular tufts suggests these cells are modulating the vascular growth in response to ischemia.
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