Related Experiment Video
Updated: May 26, 2026
Retinal Explant of the Adult Mouse Retina as an Ex Vivo Model for Studying Retinal Neurovascular Diseases
Published on: December 9, 2022
Axitinib modulates hypoxia-induced blood-retina barrier permeability and expression of growth factors
Marcus Kernt1, Sarah Thiele, Raffael G Liegl
1Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany. marcus.kernt@med.uni-muenchen.de
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.
Insights
Axitinib, a multikinase inhibitor, reduces vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) expression. This drug shows promise in treating diabetic macular edema by mitigating hypoxia-induced effects on retinal cells.
Area of Science:
- Ophthalmology
- Cell Biology
- Pharmacology
Background:
- Diabetic macular edema involves increased vascular permeability and altered growth factor expression.
- Hypoxia exacerbates RPE and HUVEC dysfunction, contributing to disease progression.
Purpose of the Study:
- To investigate axitinib's effects on VEGFR, PDGFR, and related signaling in RPE and HUVEC cells under hypoxia.
- To evaluate axitinib's potential as a therapeutic agent for diabetic macular edema.
Main Methods:
- In vitro study using primary human RPE cells and HUVECs exposed to hypoxia and axitinib.
- Assessed cell viability, tissue permeability, and expression of key proteins (occludin, ZO-1, VEGF, PDGF, VEGFRs, PDGFR-β) and their mRNAs.
- Utilized RT-PCR, ELISA, Western blotting, and immunohistochemistry.
Main Results:
- Axitinib reduced VEGFR-1/2 and PDGFR-β expression.
- Hypoxia decreased cell viability and tight junction proteins (occludin, ZO-1) while increasing permeability and VEGF/PDGF levels.
- Axitinib significantly counteracted hypoxia-induced detrimental effects in both cell types.
Conclusions:
- Axitinib effectively inhibits key signaling pathways implicated in diabetic macular edema.
- The drug's ability to reduce hypoxia-induced damage suggests potential therapeutic value for this condition.
