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

Experimental Eye Research
Michaela DithmerAlexa Klettner

Abstract

In the ophthalmological clinic, intravitreally applied antibodies or Fc-containing fusion proteins are frequently used, but the biology and pharmacokinetics of these therapeutics in the retina are not well understood. We have previously shown intracellular uptake of Fc-containing molecules in RPE cells. In this study, we investigated the involvement of Fc-receptors, both Fcγ-receptors and the neonatal Fc-receptor (FcRn) in the uptake and intracellular trafficking of the VEGF-antagonists bevacizumab, aflibercept and the anti-CD20 antibody rituximab in three different model systems, primary porcine RPE cells, ARPE-19 cells and porcine RPE/choroid explants. The expression of Fcγ-receptors was tested in primary porcine RPE cells, and the expression of Fcγ-receptors I and II could be shown in RT-PCR and qRT-PCR, while the expression of FcRn was additionally confirmed in Western blot and immunocytochemistry. All three compounds, bevacizumab, rituximab and aflibercept, were taken up into the cells and displayed a characteristic time-dependent pattern, as shown in Western blot and immunohistochemistry. The uptake was not altered by the inhibition of Fcγ-receptors using different inhibitors (TruStain FcX, genistein, R406). However, the ...Continue Reading

References

Feb 1, 1993·The Journal of Experimental Medicine·S GreenbergS C Silverstein
Feb 1, 1996·Experimental Eye Research·K C DunnL M Hjelmeland
May 1, 1997·Biochemical Society Transactions·N E SimisterC M Story
Jan 7, 1998·Journal of Molecular Biology·D E VaughnP J Bjorkman
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Feb 13, 2003·International Immunology·E Sally WardRaimund J Ober
Feb 15, 2003·Veterinary Immunology and Immunopathology·P M Schnulle, W L Hurley
May 20, 2003·Acta Ophthalmologica Scandinavica·Anne Katrine WienckeMorten La Cour
Jun 16, 2005·Molecular Cancer Therapeutics·Abhijit G BanerjeeJamboor K Vishwanatha
Jul 1, 2005·Physiological Reviews·Olaf Strauss
Aug 22, 2006·Journal of Leukocyte Biology·Zhen-Yu HuangAlan D Schreiber
Aug 26, 2006·Veterinary Immunology and Immunopathology·Songlin QiaoXuewu Li
Sep 2, 2006·The Journal of Pharmacology and Experimental Therapeutics·Sylvia BraselmannEsteban S Masuda
Jan 24, 2007·Critical Reviews in Oncology/hematology·Sophie SibérilJean-Luc Teillaud
Dec 8, 2007·Nature Reviews. Immunology·Falk Nimmerjahn, Jeffrey V Ravetch
Apr 26, 2008·Investigative Ophthalmology & Visual Science·Hyuncheol KimKarl G Csaky
Apr 29, 2008·Investigative Ophthalmology & Visual Science·Alexa Klettner, Johann Roider
Jul 15, 2009·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Alexa Karina KlettnerJohann Roider
Jan 19, 2010·Immunologic Research·Barbara Detrick, John J Hooks
Mar 2, 2011·MAbs·Charlotte Magdelaine-BeuzelinHervé Watier
Jul 19, 2011·Autoimmunity Reviews·E MiserocchiV Gerloni
Oct 20, 2012·Veterinary Immunology and Immunopathology·Bert DevriendtEric Cox
Apr 30, 2013·Veterinary Research Communications·Christin BergAlexa Klettner
Oct 26, 2013·The British Journal of Ophthalmology·Kelly L LarkinJustine R Smith
Jan 25, 2014·The British Journal of Ophthalmology·Sylvie JulienUlrich Schraermeyer
Feb 20, 2014·Investigative Ophthalmology & Visual Science·Michael B PownerMarcus Fruttiger
Jul 19, 2014·The British Journal of Ophthalmology·Alexa KlettnerJohann Roider
Dec 24, 2014·Experimental Eye Research·Shereen Hassan Aboul NagaAlexa Klettner
Mar 1, 2015·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Cornelia Volz, Diana Pauly

❮ Previous
Next ❯

Citations

Oct 19, 2016·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Tatjana TaubitzUlrich Schraermeyer
Oct 28, 2018·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Heidrun L DeisslerGabriele E Lang
Jul 28, 2020·Experimental Eye Research·Heidrun L DeisslerGabriele E Lang
Apr 4, 2021·International Journal of Molecular Sciences·Timothy Qi, Yanguang Cao
Mar 10, 2018·Experimental Eye Research·Johann SchottlerAlexa Klettner
May 18, 2021·Current Eye Research·Anna BrinkmannAlexa Klettner
Jul 6, 2021·Journal of Ophthalmology·B SobolewskaF Ziemssen
Oct 14, 2021·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Julia HildebrandtAlexa Klettner
Jul 20, 2020·Current Drug Metabolism·Xiaoxing WangPengmei Li

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.