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Michal Hausfater, Alexander I. Son, Renping Zhou; Ephrin-A5 as a Regulator Of Angiogenesis During Development As Well As Oxygen-induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3121.
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Angiogenesis, the formation of new blood vessels, is controlled by the balance of stimulating and inhibiting factors. Disturbing this balance causes abnormal blood vessel growth and prevents healing and regeneration. The Eph receptor tyrosine kinases and their ligands, the ephrins, have been recently shown to play a role in angiogenesis. Here, we investigate the role of ephrin-A5 in physiological postnatal retinal angiogenesis as well as oxygen-induced neovascularization.
Pathologic retinal vaso-obliteration and neovascularization were analyzed in a model of oxygen-induced retinopathy. Wild type and ephrin-A5-null neonatal mice were exposed to 75% oxygen from P7 to P12 followed by normoxia exposure from P12 to P17. Retinas were isolated, flatmounted and stained with isolectin-B4 at P12 or P17 for retinal vaso-obliteration and neovascularization analysis respectively. VEGF and VEGFR2 retinal mRNA and protein levels post-exposure to hyperoxia are also being analyzed using RT-PCR and western blot analysis.In addition, developmental retinal neovascularization from P0, P2, P4 and P6 wild type and ephrin-A5-null mice were analyzed using retinal flatmounts.
Ephrin-A5-null mice exhibited enhanced sensitivity to oxygen-induced vaso-obliteration and increased retinal neovascularization during oxygen-induced retinopathy compared to wild type mice. Upon termination of the oxygen exposure, P12 retinas from null mice had a significantly larger avascular area relative to the whole retina when compared to wild type mice. In addition, after 5 days of hypoxia, P17 retinas from null mice had a larger relative neovascular area. Consistant with an ephrin-A5 function in restricting angiogenesis, retinal vessels in ephrin-A5-null mice expand from the center toward the retinal periphery at a faster rate compared to wild type mice during development.
These findings indicate that ephrin-A5, a GPI-linked ligand of the Eph-A receptor family, is an important mediator of both pathological and physiological angiogenesis.
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