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VEGF antagonists decrease barrier function of retinal pigment epithelium in vitro: possible participation of
Yoko Miura1, Alexa Klettner, Johann Roider
1Department of Ophthalmology, University of Kiel, Kiel, Germany. ymiura@ophthalmol.uni-kiel.de
Investigative Ophthalmology & Visual Science
|May 4, 2010
Summary
VEGF antagonists like bevacizumab and ranibizumab may impair retinal pigment epithelium barrier function. Triamcinolone acetonide (TA) shows protective effects, potentially stabilizing RPE integrity.
Area of Science:
- Ophthalmology
- Cell Biology
- Pharmacology
Background:
- The retinal pigment epithelium (RPE) forms a critical barrier in the eye.
- Vascular Endothelial Growth Factor (VEGF) antagonists are used to treat neovascular eye diseases.
- Understanding their impact on RPE barrier function is crucial.
Purpose of the Study:
- To investigate how VEGF antagonists affect RPE barrier integrity.
- To explore the underlying mechanisms, including glutathione levels and glucose conditions.
- To assess the potential protective role of triamcinolone acetonide (TA).
Main Methods:
- Porcine RPE cells were treated with bevacizumab or ranibizumab.
- Transepithelial flux of FITC-dextran was measured to assess permeability.
- Intracellular reduced glutathione (GSH) levels were analyzed under varying glucose conditions.
- The effects of TA and GSH depletion (using BSO) were examined.
Main Results:
- Both bevacizumab and ranibizumab increased RPE permeability, with bevacizumab showing a more significant and prolonged effect.
- VEGF antagonists reduced intracellular GSH levels, particularly under low-glucose conditions.
- GSH depletion was linked to increased RPE permeability.
- TA inhibited the permeability increase induced by VEGF antagonists.
Conclusions:
- Bevacizumab and ranibizumab can compromise RPE barrier function.
- Behavicizumab demonstrates a stronger and longer-lasting impact on RPE permeability.
- Combining VEGF antagonists with TA may offer a protective strategy for maintaining RPE integrity.
