Wheeler-Schilling T H, Kohler K, Sautter M, Guenther E
Department of Pathophysiology of Vision and Neuro-ophthalmology, Division of Experimental Ophthalmology, University Eye Hospital, Tuebingen, Germany.
Eur J Neurosci. 1999 Oct;11(10):3387-94. doi: 10.1046/j.1460-9568.1999.00787.x.
In addition to its function as a peripheral hormone, angiotensin II (AngII) has been shown to act as a neuromodulator in various brain regions. AngII effects are mediated by two major AngII receptor subtypes, AT1 and AT2, and different AT1 receptor isoforms AT1A and AT1B are described in rat brains. The purpose of the present study was to analyse the expression pattern of AT receptors in different parts of the rat eye with special emphasis on the retina. Specific primers were constructed and the gene expression of AngII receptor subtypes was investigated by means of reverse transcription-polymerase chain reaction (RT-PCR). An antibody was used for cellular localization of AT1 receptor in the retina. AT2 receptor mRNA was localized by in situ hybridization (ISH). We examined the retinas of different developmental stages as well as non-neuronal ocular tissues, e.g. choroid and anterior uveal tract of rats (Brown Norway and Wistar strain), for the gene expression of AT receptors. Our results show that AT1A and AT2 mRNAs are expressed in rat choroid, iris/ciliary body and retinas, whereas AT1B mRNA is not expressed in the retina but in all other ocular tissues under investigation. AT1 receptor immunohistochemistry of the retina showed strong labelling in the ganglion cell layer (GCL), and some cells in the inner nuclear layer (INL), suggesting putative ganglion cell but also amacrine cell labelling. In the retina, ISH for AT2 mRNA revealed labelling in the GCL and a faint labelling in the inner nuclear layer. No AT2 ISH-signal was found in the other ocular tissues. These data suggest that there is a specific distribution pattern of AT receptors in rat ocular tissues, especially in the retina. The expression of AT receptors on retinal ganglion cells confirms the AngII action on these cell types and supports the role of AngII as a retinal neurotransmitter or neuromodulator.
除了作为一种外周激素发挥作用外,血管紧张素II(AngII)已被证明在各个脑区作为神经调质起作用。AngII的作用由两种主要的AngII受体亚型AT1和AT2介导,并且在大鼠脑中描述了不同的AT1受体亚型AT1A和AT1B。本研究的目的是分析大鼠眼不同部位AT受体的表达模式,特别着重于视网膜。构建了特异性引物,并通过逆转录 - 聚合酶链反应(RT-PCR)研究了AngII受体亚型的基因表达。使用一种抗体对视网膜中的AT1受体进行细胞定位。通过原位杂交(ISH)对AT2受体mRNA进行定位。我们检查了不同发育阶段的视网膜以及非神经元性眼组织,例如大鼠(棕色挪威品系和Wistar品系)的脉络膜和前葡萄膜,以检测AT受体的基因表达。我们的结果表明,AT1A和AT2 mRNA在大鼠脉络膜、虹膜/睫状体和视网膜中表达,而AT1B mRNA在视网膜中不表达,但在所研究的所有其他眼组织中表达。视网膜的AT1受体免疫组织化学显示在神经节细胞层(GCL)有强烈标记,在内核层(INL)有一些细胞有标记,提示可能标记神经节细胞以及无长突细胞。在视网膜中,AT2 mRNA的ISH显示在GCL有标记,在内核层有微弱标记。在其他眼组织中未发现AT2 ISH信号。这些数据表明大鼠眼组织中存在AT受体的特定分布模式,尤其是在视网膜中。视网膜神经节细胞上AT受体的表达证实了AngII对这些细胞类型的作用,并支持AngII作为视网膜神经递质或神经调质的作用。