Transcriptional characterization of human and mouse choroidal neovascularization identifies fibroblast growth factor inducible-14 as a novel mediator of neo-vascular age-related macular degeneration

Visual outcome of patients with neovascular age-related macular degeneration has significantly improved during the last years as a result of anti-VEGF therapy. However, some patients show persistent exudation and decreasing visual acuity despite recurrent anti-VEGF injections, indicating a role of other proangiogenic mediators. The present study applied transcriptional profiling of human and mouse CNV membranes each with reference to healthy control tissue to identify novel mediators of CNV. Following this approach, the study identifies Fibroblast growth factor induci-ble-14 (FN14) as a novel phylogenetically conserved mediator of CNV. Blocking the pathway by intravitreal injection of an FN14 decoy receptor modulates the cytokine profile - most notably IL-6 - and leads to a significant and IL-6 mediated reduction of CNV size in vivo. These results identify FN14 as a promising new therapeutic target for neovascular AMD, which may potentially be beneficial in patients with exudative AMD with special regard to anti-VEGF resistant cases. Overall design: MACE RNA sequencing of 6 mouse CNV and 6 mouse RPE/choroid control samples as well as 4 human CNV membranes and 4 human control RPE/choroid samples.