FcRn receptor-mediated pharmacokinetics of therapeutic IgG in the eye

Mol Vis. 2009 Dec 16;15:2803-12.

Abstract

Purpose: The goal of this study was to determine the role of the neonatal Fc (FcRn) receptor in eliminating intravitreally administered full-length immunoglobulin G (IgG) across the blood-retinal barrier.

Methods: FcRn receptor expression in normal and laser photocoagulated retinas was compared quantitatively by real-time RT-PCR. The distribution of intravitreally administered full-length IgG was investigated and compared in wild-type and FcRn knockout mouse eyes as well as normal and laser-photocoagulated rat eyes at several time points. Additionally, the pharmacokinetics of intravitreally injected full-length IgG and chicken immunoglobulin Y (IgY) was compared in the normal rat retina.

Results: Intravitreally administered full-length IgG overcame the inner limiting membrane and diffused into the deeper retinal structures in both normal and laser-photocoagulated retinas. Interestingly, IgG was eliminated across the blood-retinal barrier into the blood system in the normal retina, whereas IgY was not. In addition, full-length IgGs did not penetrate across the blood-retinal barrier in the FcRn knockout mouse. Intravitreally injected IgGs were eliminated into the blood system more rapidly in laser-photocoagulated eyes when compared to normal control eyes because of FcRn receptor upregulation in the laser-photocoagulated retina.

Conclusions: FcRn plays an important role in eliminating intravitreally administered full-length IgGs across the blood-retina barrier into the systemic blood system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Chickens
  • Drug Administration Routes
  • Eye / metabolism*
  • Fluorescent Dyes / metabolism
  • Immunoglobulins / metabolism
  • Laser Coagulation
  • Male
  • Mice
  • Mice, Knockout
  • Rats
  • Rats, Inbred BN
  • Receptors, Fc / metabolism*
  • Retina / metabolism

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Fluorescent Dyes
  • IgY
  • Immunoglobulins
  • Receptors, Fc
  • Bevacizumab