Krajacic Predrag, Qian Ying, Hahn Paul, Dentchev Tzvete, Lukinova Nina, Dunaief Joshua L
F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Invest Ophthalmol Vis Sci. 2006 Jul;47(7):3129-34. doi: 10.1167/iovs.05-1601.
Menkes and Wilson diseases are associated with retinal degeneration. The Menkes and Wilson genes are homologous copper transporters, but differences in their expression pattern lead to different disease manifestations. To determine whether the Wilson and Menkes genes may act locally in the retina, this study was undertaken to assess retinal Wilson and Menkes expression and localization.
RT/PCR was used to test for the presence of Wilson and Menkes mRNAs in mouse and human retinas and retinal pigment epithelial cell lines. The Menkes and Wilson proteins were immunolocalized in human and mouse retinas and in the ARPE-19 cell line.
The Menkes mRNA and protein were present in the RPE and neurosensory retina whereas the Wilson mRNA and protein were limited to the RPE. In the RPE, both proteins localized to the Golgi. Increased copper concentration led to relocalization of the Wilson protein to a diffuse cytoplasmic distribution.
Both the Menkes and Wilson proteins are present in the RPE. Since the RPE is a blood-brain barrier, these proteins most likely regulate not only their own copper levels but also copper levels of the overlying photoreceptors. Because the Wilson protein delivers copper to the ferroxidase ceruloplasmin in the liver, it is likely that the Wilson and/or Menkes proteins provide copper to ceruloplasmin made in the RPE. Retinopathy in Wilson and Menkes diseases may result not only from abnormal systemic copper levels but also from loss of retinal Wilson or Menkes protein.
门克斯病和威尔逊病与视网膜变性相关。门克斯基因和威尔逊基因是同源铜转运蛋白，但它们表达模式的差异导致了不同的疾病表现。为了确定威尔逊基因和门克斯基因是否可能在视网膜局部发挥作用，本研究旨在评估视网膜中威尔逊基因和门克斯基因的表达及定位。
采用逆转录/聚合酶链反应（RT/PCR）检测小鼠和人类视网膜及视网膜色素上皮细胞系中威尔逊基因和门克斯基因mRNA的存在情况。对门克斯蛋白和威尔逊蛋白进行免疫定位，观察其在人类和小鼠视网膜以及ARPE - 19细胞系中的分布。
门克斯基因的mRNA和蛋白存在于视网膜色素上皮（RPE）和神经感觉视网膜中，而威尔逊基因的mRNA和蛋白仅局限于RPE。在RPE中，两种蛋白均定位于高尔基体。铜浓度升高导致威尔逊蛋白重新定位至弥漫性胞质分布。
门克斯蛋白和威尔逊蛋白均存在于RPE中。由于RPE是血脑屏障的一部分，这些蛋白很可能不仅调节自身的铜水平，还调节上方光感受器的铜水平。因为威尔逊蛋白在肝脏中向铁氧化酶铜蓝蛋白输送铜，所以威尔逊蛋白和/或门克斯蛋白可能为RPE中产生的铜蓝蛋白提供铜。威尔逊病和门克斯病中的视网膜病变可能不仅源于全身铜水平异常，还源于视网膜中威尔逊蛋白或门克斯蛋白的缺失。
