Kim Hyuncheol, Robinson Shaun B, Csaky Karl G
Department of Chemical and Biomolecular Engineering, Sogang University, Seoul, South Korea.
Mol Vis. 2009 Dec 16;15:2803-12.
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.
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.
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.
FcRn plays an important role in eliminating intravitreally administered full-length IgGs across the blood-retina barrier into the systemic blood system.
本研究的目的是确定新生儿Fc（FcRn）受体在跨越血视网膜屏障清除玻璃体内注射的全长免疫球蛋白G（IgG）中的作用。
通过实时逆转录聚合酶链反应（RT-PCR）定量比较正常视网膜和激光光凝视网膜中FcRn受体的表达。在多个时间点，研究并比较野生型和FcRn基因敲除小鼠眼以及正常和激光光凝大鼠眼中玻璃体内注射的全长IgG的分布。此外，还比较了正常大鼠视网膜中玻璃体内注射全长IgG和鸡免疫球蛋白Y（IgY）的药代动力学。
玻璃体内注射的全长IgG在正常视网膜和激光光凝视网膜中均克服了内界膜并扩散到更深层的视网膜结构中。有趣的是，在正常视网膜中，IgG通过血视网膜屏障进入血液系统而被清除，而IgY则不会。此外，在FcRn基因敲除小鼠中，全长IgG不能穿透血视网膜屏障。与正常对照眼相比，由于激光光凝视网膜中FcRn受体上调，玻璃体内注射的IgG在激光光凝眼中更快地被清除到血液系统中。
FcRn在跨越血视网膜屏障将玻璃体内注射的全长IgG清除到全身血液系统中起重要作用。
