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-ß), 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-ß, 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-ß. 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.
Subject(s)
Blood-Retinal Barrier/drug effects , Blood-Retinal Barrier/physiopathology , Cell Membrane Permeability/drug effects , Imidazoles/pharmacology , Indazoles/pharmacology , Intercellular Signaling Peptides and Proteins/metabolism , Adult , Aged , Axitinib , Blood-Retinal Barrier/metabolism , Cell Hypoxia , Cell Survival/drug effects , Cells, Cultured , Diabetic Retinopathy/therapy , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/pathology , Humans , Imidazoles/therapeutic use , Indazoles/therapeutic use , Intercellular Signaling Peptides and Proteins/genetics , Macular Edema/therapy , Middle Aged , Pigment Epithelium of Eye/cytology , Pigment Epithelium of Eye/drug effects , Pigment Epithelium of Eye/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor, Platelet-Derived Growth Factor beta/genetics , Receptor, Platelet-Derived Growth Factor beta/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-1/genetics , Vascular Endothelial Growth Factor Receptor-1/metabolismABSTRACT
A novel method for cervicofacial rejuvenation by submandibular neck lifting with platysma resection is presented. Between 2003 and 2009 we performed submandibular neck lifting in 18 cases. This technique is an isolated but efficient procedure for lifting of the neck. An additional advantage might be the possibility of doing the procedure with tumescence local anesthesia. In all cases, satisfactory aesthetic results were achieved.
