UCL Institute of Ophthalmology, University College London, London, United Kingdom.
Invest Ophthalmol Vis Sci. 2014 Mar 19;55(3):1607-15. doi: 10.1167/iovs.13-12574.
The neonatal Fc receptor (FcRn) plays a critical role in the homeostasis and degradation of immunoglobulin G (IgG). It mediates the transport of IgG across epithelial cell barriers and recycles IgG in endothelial cells back into the bloodstream. These functions critically depend on the binding of FcRn to the Fc domain of IgG. The half-life and distribution of intravitreally injected anti-VEGF molecules containing IgG-Fc domains might therefore be affected by FcRn expressed in the eye. In order to establish whether FcRn-Fc(IgG) interactions may occur in the eye, we studied the mRNA and protein distribution of FcRn in postmortem ocular tissue.
We used qPCR to study mRNA expression of the transmembrane chain of FcRn (FCGRT) in retina, optic nerve, RPE/choroid plexus, ciliary body/iris plexus, lens, cornea, and conjunctiva isolated from mouse, rat, pig, and human postmortem eyes and used immunohistochemistry to determine the pattern of FcRn expression in FCGRT-transgenic mouse and human eyes.
In all four tested species, Fcgrt mRNA was expressed in the retina, RPE/choroid, and the ciliary body/iris, while immunohistochemistry documented FcRn protein expression in the ciliary body epithelium, macrophages, and endothelial cells in the retinal and choroidal vasculature.
Our results demonstrate that FcRn has the potential to interact with IgG-Fc domains in the ciliary epithelium and retinal and choroidal vasculature, which might affect the half-life and distribution of intravitreally injected Fc-carrying molecules.
新生儿 Fc 受体（FcRn）在免疫球蛋白 G（IgG）的体内平衡和降解中发挥关键作用。它介导 IgG 穿过上皮细胞屏障的转运，并将内皮细胞中的 IgG 再循环回血液中。这些功能严重依赖于 FcRn 与 IgG 的 Fc 结构域结合。因此，眼内注射含有 IgG-Fc 结构域的抗 VEGF 分子的半衰期和分布可能受到眼内表达的 FcRn 的影响。为了确定 FcRn-Fc（IgG）相互作用是否可能发生在眼睛中，我们研究了眼组织中 FcRn 的 mRNA 和蛋白分布。
我们使用 qPCR 研究了从鼠、大鼠、猪和人死后眼睛中分离的视网膜、视神经、RPE/脉络膜丛、睫状体/虹膜丛、晶状体、角膜和结膜中的 FcRn 跨膜链（FCGRT）的 mRNA 表达，并使用免疫组织化学确定了 FCGRT 转基因小鼠和人眼的 FcRn 表达模式。
在所有四种测试的物种中，Fcgrt mRNA 在视网膜、RPE/脉络膜和睫状体/虹膜中表达，而免疫组织化学记录了 FcRn 蛋白在睫状体上皮细胞、巨噬细胞和视网膜和脉络膜血管中的内皮细胞中的表达。
我们的结果表明，FcRn 有可能与睫状上皮细胞和视网膜及脉络膜血管中的 IgG-Fc 结构域相互作用，这可能影响眼内注射的 Fc 携带分子的半衰期和分布。
