Axitinib modulates hypoxia-induced blood-retina barrier permeability and expression of growth factors

作者：Kernt Marcus^*; Thiele Sarah; Liegl Raffael G; Kernt Barbara; Eibl Kirsten; Haritoglou Christos; Ulbig Michael W; Kampik Anselm

来源：Growth Factors, 2012, 30(1): 49-61.

DOI：10.3109/08977194.2011.639300

• Diabetic retinopathy
• diabetic macular edema
• bevacizumab
• VEGF
• growth factors
• multikinase inhibitors
• pazopanib
• axitinib

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-beta), 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-beta, 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-beta. 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.

• 出版日期2012-2