The role of Fc-receptors in the uptake and transport of therapeutic antibodies in the retinal pigment epithelium

摘要: In the ophthalmological clinic, intravitreally applied antibodies or Fc-containing fusion proteins are frequently used, but biology and pharmacokinetics of these therapeutics in retina not well understood. We have previously shown intracellular uptake molecules RPE cells. this study, we investigated involvement Fc-receptors, both Fcγ-receptors neonatal Fc-receptor (FcRn) trafficking VEGF-antagonists bevacizumab, aflibercept anti-CD20 antibody rituximab three different model systems, primary porcine cells, ARPE-19 cells RPE/choroid explants. The expression was tested I II could be RT-PCR qRT-PCR, while FcRn additionally confirmed Western blot immunocytochemistry. All compounds, aflibercept, were taken up into cells displayed a characteristic time-dependent pattern, as immunohistochemistry. altered by inhibition using inhibitors (TruStain FcX, genistein, R406). However, with an antagonistic reduced IgG (rituximab) (bevacizumab, rituximab). Colocalisations between compounds myosin7a found. addition, limited colocalization triple localization compound, detected, indicating role mediated transport. colocalizations restricted to small fractions compounds. Furthermore, is mainly found membrane section, where only minute amounts seen, suggesting interaction. An apical choroidal transport through can Inhibition increases amount bevacizumab on side, recycling bevacizumab. conclusion, our data indicate for FcRn, Fcγ-receptors, function retina.