gms | German Medical Science

Background: Bevacizumab and aflibercept are widely used intervitreal therapeutics in age-related macular degeneration. Both contain an Fc-fragment, which has been implicated to participate in pharmacokinetics and intracellular uptake of these molecules. In this study, we investigated the involvement of Fc-receptors (Fc-gamma, neonatal) in the uptake of these VEGF-inhibitors in the retinal pigment Epithelium (RPE).

Methods: Primary porcine RPE cell cultures, porcine RPE/choroid organ explants and the human cell line Arpe19 was used in this study. Uptake of bevacizumab (250 µg/ml) and aflibercept (250µg/ml, 500 µg/ml) was investigated in Western blot, cellular localization in subcellular fractioning and immune fluorescence. Fc-receptors were inhibited with genistein, R104, FcX, or anti-FcRn antibodies.

Results: The inhibition of Fc-gamma receptors does not alter cellular uptake of bevacizumab or aflibercept. Some influence of the neonatal Fc-receptor can be found for bevacizumab but not for aflibercept. Both bevacizumab and aflibercept are mainly found in the cytoskeleton fraction of RPE cells. Colocalizations of bevacizumab and alfibercept with the neonatal Fc-receptor together with the motor protein Myosin7a can be found intracellularly for both compounds. Most of the neonatal Fc-receptor can be found in membranes, indicating the interaction between neonatal Fc-receptor and the therapeutics to be temporary for a definite region in intracellular trafficking.

Conclusion: Fc-gamma receptors do not seem to be important for bevacizumab or aflibercept uptake. Intracellular transport seems to be partly mediated by the neonatal Fc-receptor.