Echinomycin mitigates ocular angiogenesis by transcriptional inhibition of the hypoxia-inducible factor-1

Echinomycin (EKN), an inhibitor of hypoxia-inducible factor (HIF)-1 DNA-binding activity, has been implied as a possible therapeutic agent in ischemic diseases. Here, we assess EKN hypoxia-driven responses vitro using human primary adult retinal pigment epithelium cells (aRPE) and endothelial (hREC), vivo the laser-induced mouse choroidal neovascularization (CNV) model. Effects on hypoxia-mediated pathways aRPE were analyzed by Western blotting for HIF-1α protein, quantitative PCR HIF-target genes, proteome array soluble angiogenic factors. In inhibition angiogenesis was determined hREC. CNV, model HIF-associated ocular neovascularization. CNV lesion area fundus fluorescein angiography. treated with showed hypoxia-dependent significantly decreased cell recovery wound healing assay. These results supported lower levels HIF-mediated transcripts detected hypoxic compared non-treated controls, confirmed profiler hREC exposed to EKN-conditioned medium displayed reduced sprouting angiogenesis. Mice intravitreally injected vascular when equivalent aflibercept, or vehicle-treated controls. Our data proposes potent which could have future implications treatment patients neovascular age-related macular degeneration.