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AbstractP 256 Delayed development of retinal vessel network in alpha 2B adrenergic receptor knock-out mice Hua J.1, Muthig V.2, Gross N.1, Lange C.1, Martin G.1, Hansen L. L.1, Hein L.2, Agostini H. T.1
1University Eye Hospital, Freiburg, 2Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg Objective: Alpha 2 adrenergic receptors (Adra2) mediate diverse biological effects of the endogenous catecholamines epinephrine and norepinephrine. Subtype Adra2b was found to be essential for placental vascular development, whereas the other two subtypes Adra2a and Adra2c are presynaptic feedback regulators of sympathetic nerves. To determine its role in vasculogenesis and angiogenesis, we studied the development of retinal vasculature in Adra2b knock-out (Adra2b-/-) and wild type mice.
Methods: Adra2b-/- and C57Bl/6 mice underwent intraventrical perfusion with FITC-dextran solution. After enucleation, retinal flat mounts were prepared at different time points: first (p1), fourth (p4), seventh (p7), and tenth (p10) postnatal day (n=4 per time point and genotype). The ratio of vascularised area to total retinal area was taken as an index for the vascularisation progress.
Results: A significant delay of vascularisation in Adra2b-/- mice was found on p4 and p7 as compared to the control group. Both in Adra2b-/- mice and wt mice about 5% of the central retina is vascularised on p1. The vessel network reaches the edge of the peripheral retina on p10 in both genotypes.
Conclusions: The development of the murine retinal vasculature is influenced by Adra2b. However, the cellular mechanism involved remains unknown. Recent studies indicated that activation of the mitogen-activated protein kinase (MAP kinase) pathway by Adra2 is required for placenta and yolk-sac vascular development. Future studies will have to address whether the findings derived from knockout mice are relevant for human physiology and retinal disease.
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