Key result
Anti-VEGF treatment completely suppressed hVEGF in rabbit vitreous for 28 days, with aflibercept demonstrating the greatest inhibitory effect on ANG2 levels.
Why the study?
Anti-VEGF therapies treat retinal angiogenesis and vascular permeability, but multiple other pathways including ANG1 and ANG2 are also involved.
Do anti-VEGF agents suppress ANG2 protein and ANGPT2 mRNA in a rabbit retinal vascular hyperpermeability model?
Do anti-VEGF agents suppress ANG2 protein and ANGPT2 mRNA in a rabbit retinal vascular hyperpermeability model?
Anti-VEGF agents, particularly aflibercept, suppress ANG2 protein and ANGPT2 mRNA in a rabbit model of retinal vascular hyperpermeability, suggesting benefits beyond direct VEGF binding.
May extend anti-VEGF effects to angiopoietin-2 suppression in preclinical models; leaves open human retinal translation.
Purpose: Anti-vascular endothelial growth factor (anti-VEGF) therapies, which attenuate the capacity of VEGF to bind to VEGF receptors, are standard-of-care options for various retinal disorders that are characterized by pathologic retinal angiogenesis and vascular permeability. Multiple receptors and ligands have also been reported as being involved in these pathways, including angiopoietin-1 (ANG1) and angiopoietin-2 (ANG2). Methods: Electrochemiluminescence immunoassays were used to detect human VEGF (hVEGF), as well as rabbit ANG2 and basic fibroblast growth factor protein levels in vitreous samples derived from a study evaluating the efficacy of the anti-VEGF agents ranibizumab, aflibercept, and brolucizumab in an hVEGF165-induced rabbit retinal vascular hyperpermeability model. Results: hVEGF was completely suppressed in rabbit vitreous after anti-VEGF treatment for 28 days. ANG2 protein in vitreous and ANGPT2 mRNA in retina tissue were similarly suppressed, although the anti-VEGF agents do not directly bind to ANG2. Aflibercept demonstrated the greatest inhibitory effect in ANG2 levels in vitreous, which correlated with strong, durable suppression of intraocular hVEGF levels. Conclusions: This study explored the effects of anti-VEGF therapies beyond direct binding of VEGF by evaluating protein levels and the expression of target genes involved in angiogenesis and associated molecular mechanisms in the rabbit retina and choroid. Translational Relevance: In vivo data suggest that anti-VEGF agents currently used for the treatment of retinal diseases could provide beneficial effects beyond direct binding of VEGF, including suppression of ANG2 protein and ANGPT2 mRNA.
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Lange et al. (2023) studied hVEGF165-induced rabbit retinal vascular hyperpermeability. Anti-VEGF agents (ranibizumab, aflibercept, and brolucizumab) was evaluated on hVEGF, ANG2, and basic fibroblast growth factor protein levels in vitreous and ANGPT2 mRNA in retina tissue. Anti-VEGF treatment completely suppressed hVEGF in rabbit vitreous for 28 days, with aflibercept demonstrating the greatest inhibitory effect on ANG2 levels.
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