title: Axitinib modulates hypoxia-induced blood-retina barrier permeability and expression of growth factors.
abstract: This study investigates the effects of the multikinase inhibitor axitinib on the expression of vascular endothelial growth factor (VEGF) receptors 1/2 (VEGFR-1/2) and platelet-derived growth factor (PDGF) receptor beta (PDGFR-β), hypoxia-induced increased tissue permeability, occludin, zonula occludens protein 1 (ZO-1), VEGF-A, and PDGF expression of human retinal pigment epithelial (RPE) cells and human umbilical vein endothelial cells (HUVECs). Primary human RPE cells and HUVECs were exposed to hypoxia and axitinib. Viability of cells, tissue permeability, and expression of occludin, ZO-1, VEGF, PDGF, VEGFR-1/2 and PDGFR-β, and their mRNAs, were investigated by reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry. Treatment with axitinib reduced expression of VEGFR-1/2 and PDGFR-β. Hypoxia decreased cell viability, occludin, and ZO-1 expression and increased tissue permeability, expression, and secretion of VEGF and PDGF. Axitinib significantly reduced hypoxia-induced effects on HUVEC and RPE cells. Our in vitro results suggest that axitinib may have promising properties as a potential treatment for diabetic macular edema.
authors.affiliation: Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany. marcus.kernt@med.uni-muenchen.de
authors.forename: Marcus
authors.initials: M
authors.lastname: Kernt
authors.forename: Sarah
authors.initials: S
authors.lastname: Thiele
authors.forename: Raffael G
authors.initials: RG
authors.lastname: Liegl
authors.forename: Barbara
authors.initials: B
authors.lastname: Kernt
authors.forename: Kirsten
authors.initials: K
authors.lastname: Eibl
authors.forename: Christos
authors.initials: C
authors.lastname: Haritoglou
authors.forename: Michael W
authors.initials: MW
authors.lastname: Ulbig
authors.forename: Anselm
authors.initials: A
authors.lastname: Kampik
mesh_terms: D000328:Adult; D000368:Aged; D000077784:Axitinib; D001813:Blood-Retinal Barrier / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D015687:Cell Hypoxia; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000628:therapy; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007191:Indazoles / Q000494:pharmacology* / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008269:Macular Edema / Q000628:therapy; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D007093:Imidazoles; D007191:Indazoles; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000077784:Axitinib; D020797:Receptor, Platelet-Derived Growth Factor beta; D040281:Vascular Endothelial Growth Factor Receptor-1