Tissue origin of endothelial cells determines immune system modulation and regulation of HIF1a-, TGFß- and VEGF- signaling

Dysfunction of the blood retinal barriers and/or proliferation of retinal and choroidal endothelial cells are caused by late stages of diabetic retinopathy (DR) and neovascular age-related macular degeneration (nAMD). To elucidate endothelial-derived pathomechanisms in DR and nAMD, we established immortalized mouse cell lines of retinal (REC), choroidal (ChEC) and brain (BEC)endothelial cells. We compared the functional and transcriptomic state of these cells depending on their tissue origin. Intriguingly, activation of the wingless-type MMTV integration site (Wnt)/ß-catenin signaling pathway restored barrier properties in BEC and REC, but increased permeability of ChEC. Transcriptome profiling showed that the immune system and pathways such as hypoxia-inducible factor (HIF) 1/2a-, transforming growth factor (TGF) ß- and vascular endothelial growth factor (VEGF) were differentially regulated among endothelial cells. These findings significantly increase the understanding of the vascular biology of endothelial cells, highlighting the fact that depending on their tissue origin, their contribution to vascular pathologies such as DR or nAMD may vary. Overall design: Immortalised endothelial cells of different origin were sequenced by the nanopore long-read technology.