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Irina Semkova, Philipp S. Muether, Mark Kuebbeler, Klaus L. Meyer, Norbert Kociok, Antonia M. Joussen; Recruitment of Blood-Derived Inflammatory Cells Mediated via Tumor Necrosis Factor-α Receptor 1b Exacerbates Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2011;52(9):6101-6108. doi: 10.1167/iovs.10-5996.
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Tumor necrosis factor (TNF)-α contributes to inflammation-associated angiogenesis, and TNF-α receptor 1b is selectively expressed on immuno-competent and endothelial cells. This study investigated the role of TNF-α receptor 1b in the recruitment of circulating inflammatory cells and the development of choroidal neovascularization (CNV).
Lethally irradiated Tnfrsf1b−/− mice and their wild-type (WT) controls were transplanted with whole adult bone marrow (BM) cells, competent for both TNF-α receptors 1a and 1b (gfp+ labeled), as well as with BM cells deficient for TNF-α receptor 1b. One month after transplantation CNV was induced by laser damage of Bruch's membrane. Pathologic angiogenesis was estimated qualitatively and quantitatively by histology on choroidal flatmounts and paraffin cross sections. Macrophage invasion was investigated by immunochemistry.
One month after transplantation the reconstitution rate measured by FACS analysis was >80% in gfp+-chimeric mice. Two weeks after laser injury reduced gfp+-cell invasion to the laser scars and decreased pathologic angiogenesis were observed in Tnfrsf1b−/− versus WT recipients. Approximately 70% of the invaded gfp+ cells were labeled with macrophage marker F4/80. Transplantation of TNF-α receptor 1b–deficient BM cells in WT recipients reduced the CNV lesion compared with WT and Tnfrsf1b−/− recipients that received TNF-α receptor–competent BM cells. Transplantation of receptor 1b–deficient cells to Tnfrsf1b−/− recipients further reduced the degree of CNV formation.
Signals through TNF-α receptor 1b expressed on BM -derived inflammatory cells mediate an increased inflammatory cell invasion and enhanced angiogenic response after laser-induced rupture of Bruch's membrane.
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