FcRn receptor-mediated pharmacokinetics of therapeutic IgG in the eye.
OBJECTIVE
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.
Kim
Hyuncheol
H
Department of Chemical and Biomolecular Engineering, Sogang University, Seoul, South Korea. hyuncheol@sogang.ac.kr
Robinson
Shaun B
SB
Csaky
Karl G
KG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002645:Chickens; D004333:Drug Administration Routes; D005123:Eye / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism; D017075:Laser Coagulation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D011914:Rats, Inbred BN; D011961:Receptors, Fc / Q000378:metabolism*; D012160:Retina / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005456:Fluorescent Dyes; C016512:IgY; D007136:Immunoglobulins; D011961:Receptors, Fc; D000068258:Bevacizumab