Differential Role of Tumor Necrosis Factor (TNF)-α Receptors in the Development of Choroidal Neovascularization

PURPOSE. Tumor necrosis factor alpha (TNF)contributes to inflammation-associated angiogenesis. This study investigates the role of TNFreceptors 1a and 1b in the development of choroidal neovascularization (CNV). METHODS. CNV was induced in Tnfrsf1a / and Tnfrsf1b / mice with C57Bl6/J background and their wild-type (WT) (C57Bl/6J) controls by laser damage to the Bruch’s membrane. TNFexpression in RPE/choroid was determined by Western blot analysis. Pathologic angiogenesis was estimated qualitatively and quantitatively by fluorescein angiography and histology on choroidal flat mounts and paraffin cross-sections. Inflammatory cell invasion was investigated by clodronic acid depletion of circulating macrophages and immunochemistry, and the apoptotic activity was investigated by TUNEL assay and by caspase-3 and caspase-8 expression. Receptor 1b-specific Bmx/Etk kinase was detected by immunochemistry.