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Aflibercept Suppression of Angiopoietin-2 in a Rabbit Retinal Vascular Hyperpermeability Model
Claudia Lange1,2, Reimo Tetzner3,4, Tobias Strunz5,6
1Research & Development, Precision Medicine Markers, Bayer AG, Berlin, Germany.
Translational Vision Science & Technology
|May 16, 2023
Summary
Anti-vascular endothelial growth factor (anti-VEGF) therapies suppress angiopoietin-2 (ANG2) protein and ANGPT2 mRNA in retinal disease models. These findings suggest anti-VEGF treatments offer benefits beyond direct VEGF pathway inhibition.
Area of Science:
- Ophthalmology
- Molecular Biology
- Pharmacology
Background:
- Anti-vascular endothelial growth factor (anti-VEGF) therapies are standard treatments for retinal disorders.
- Pathologic retinal angiogenesis and vascular permeability involve VEGF, angiopoietin-1 (ANG1), and angiopoietin-2 (ANG2) pathways.
Purpose of the Study:
- To investigate the effects of anti-VEGF therapies beyond direct VEGF binding.
- To evaluate protein and gene expression in angiogenesis-related pathways in a rabbit model.
Main Methods:
- Used electrochemiluminescence immunoassays to measure human VEGF (hVEGF), rabbit ANG2, and basic fibroblast growth factor.
- Analyzed vitreous and retinal tissue samples from a rabbit model of hVEGF165-induced retinal vascular hyperpermeability.
Main Results:
- Anti-VEGF treatment suppressed hVEGF, ANG2 protein, and ANGPT2 mRNA in rabbit eyes.
- Aflibercept showed the most significant inhibition of ANG2 levels, correlating with sustained hVEGF suppression.
- Anti-VEGF agents do not directly bind ANG2, indicating an indirect mechanism of suppression.
Conclusions:
- Anti-VEGF therapies may exert beneficial effects by suppressing ANG2 protein and ANGPT2 mRNA.
- These findings suggest broader therapeutic mechanisms for anti-VEGF agents in retinal diseases.
