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[Basic in vitro studies on VEGF inhibition with aflibercept: similarities and differences to other VEGF-binding therapeutic proteins].

Abstract：

:Patients suffering from various retinal diseases benefit from therapies directed against the vascular endothelial growth factor (VEGF). Aflibercept (Eylea) is another VEGF-binding protein available for intravitreal injection, in addition to the antibody bevacizumab (Avastin) and the F(ab) fragment ranibizumab (Lucentis). Aflibercept's distinct structure and broader binding specificity may have clinically relevant consequences, which is supported by basic in vitro studies and observations in animal eyes. All pathological processes involving neovascularisation are driven by the dominant action of VEGF, but other factors including placenta growth factor (PlGF), a mitogenic protein for retinal endothelial cells, potentially modulate its effects. Aflibercept is an inhibitor of both VEGF and PlGF and therefore may have superior therapeutic effects in some cases. However, whether or not aflibercept's broader binding specificity or different affinities for the different VEGF-binding proteins to VEGF result in substantially diverse therapeutic efficiencies has not yet been clarified. In vitro studies confirm that aflibercept efficiently prevents or normalises VEGF-stimulation of retinal cells and disturbance of their barrier function. These experiments also show that aflibercept is taken up by important retinal cell types and affects their normal function, i.e., migration of endothelial cells and phagocytosis of pigment epithelial cells. In accordance with a role of the Fc domains of aflibercept and bevacizumab, substantial amounts of both proteins are internalised, whereas only a small portion of ranibizumab enters the cells. Internalisation and storage by ocular cells, also observed in vivo after intravitreal injection into eyes of monkeys, may result in not yet recognised side effects during long-term treatment of patients with certain VEGF-binding proteins.

journal_name

Klin Monbl Augenheilkd

journal_title

Klinische Monatsblatter fur Augenheilkunde

authors

Lang GE,Lang GK,Deissler HL

doi

10.1055/s-0034-1383142

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

295-302

issue

eissn

0023-2165

issn

1439-3999

journal_volume

232

pub_type

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[Basic in vitro studies on VEGF inhibition with aflibercept: similarities and differences to other VEGF-binding therapeutic proteins].