Subunits of the epithelial sodium channel family are differentially expressed in the retina of mice with ocular hypertension
Subunits of the epithelial sodium channel family are differentially expressed in the retina of mice with ocular hypertension
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DOI：
10.1111/j.1471-4159.2005.03177.x
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发表时间：
2005-07-01
影响因子：
4.7
通讯作者：
Enz, R
中科院分区：
文献类型：
--
作者：
Dyka, FM;May, CA;Enz, R
青光眼是一种常见的致盲性疾病，它导致视网膜神经节细胞凋亡和视神经变性。这种疾病通常与眼内压升高有关，然而，对神经节细胞死亡的分子机制知之甚少。为了鉴定导致这种病理过程的蛋白质，我们分析了DBA/2 J小鼠的视网膜基因表达，这些小鼠在6个月大时出现眼内压升高，随后出现神经节细胞丢失。在这项研究中，我们确定了上皮钠通道（ENaC）家族的亚基，这些亚基在高眼压下特异性表达。使用逆转录聚合酶链反应，我们观察到一个显着增加的α-ENaC在DBA/2 J小鼠的神经元视网膜相比，对照组动物，而β-ENaC和γ-ENaC在这个组织中检测不到。ENaC亚单位的特异性免疫血清显示在视网膜的突触和核层以及视网膜色素上皮中α-ENaC的上调。与我们的聚合酶链反应数据一致，在视网膜中没有检测到β-ENaC的特异性抗体，而γ-ENaC仅存在于高眼压下的视网膜色素上皮中。最后，在DBA/2 J小鼠的其他组织中未观察到神经元视网膜和视网膜色素上皮中的α-ENaC基因表达的增加。由于眼内压是通过眼上皮结构中的房水转运来调节的，而房水转运又与离子通量相关，因此ENaC蛋白的特异性上调可以作为防止眼内压升高的保护机制。
Glaucoma is a prevalent cause of blindness, resulting in the apoptotic death of retinal ganglion cells and optic nerve degeneration. The disease is often associated with elevated intraocular pressure, however, molecular mechanisms involved in ganglion cell death are poorly understood. To identify proteins contributing to this pathological process, we analysed the retinal gene expression of DBA/2J mice that develop an elevated intraocular pressure by the age of 6 months with subsequent ganglion cell loss. In this study, we identified subunits of the epithelial sodium channel (ENaC) family that are specifically expressed under elevated intraocular pressure. Using reverse transcriptase polymerase chain reaction we observed a significant increase of alpha-ENaC in the neuronal retina of DBA/2J mice when compared with control animals, while beta-ENaC and gamma-ENaC were not detectable in this tissue. Specific immune sera to ENaC subunits showed up-regulation of alpha-ENaC in synaptic and nuclear layers of the retina, and in the retinal pigment epithelium. Consistent with our polymerase chain reaction data, beta-ENaC was not detected by specific antibodies in the retina, while gamma-ENaC was only present in the retinal pigment epithelium under ocular hypertension. Finally, the increase of alpha-ENaC gene expression in the neuronal retina and the retinal pigment epithelium was not observed in other tissues of DBA/2J mice. Since the intraocular pressure is regulated by the transport of aqueous humour across epithelial structures of the eye that in turn is associated with ion flux, the specific up-regulation of ENaC proteins could serve as a protecting mechanism against elevated intraocular pressure.