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M. Hausfater, A. I. Son, R. Zhou; Regulation of Retinal Angiogenesis by the Eph Family Ligand Ephrin-A5. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3353.
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Retinal angiogenesis requires the careful orchestration of several factors, including vascular endothelial growth factor (VEGF), and platelet-derived growth factors (PDGF). Misregulation of these factors can result in the development of various retinopathies. The Eph receptor tyrosine kinases and their ligands, ephrins, have been recently shown to play a role in angiogenesis. Here, we examine how the interaction between ephrin-A5, VEGF and PDGF signals regulates angiogenesis.
Eyes from wild type and ephrin-A5-null mice were fixed and the retinas isolated. Retinal vessel sprouting was visualized by anti-collagen IV immunostaining at P0, P2, P4 and P6. In addition, effects of ephrin-A5 on VEGF and PDGF-induced signaling events such as Ras/MAPK activation in human umbilical vein endothelial cells (HUVECs) and multipotent mesenchymal 10T1/2 cells, have been examined. Ephrin-A5 effects on migration of HUVEC and 10T1/2 cells are also being analyzed using wound healing and transwell assays.
Retinal vessels in ephrin-A5-null mice expand from the center toward the retinal periphery at a faster rate compared to that in wild type mice during postnatal development. In vitro, ephrin-A5 protein inhibits both VEGF and PDGR-induced ERK1/2 activation.
Our studies indicate that ephrin-A5 is an anti-angiogenic factor that inhibits VEGF and PDGF-induced responses in vitro as well as retinal angiogenesis in vivo.
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