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内皮素-1与内皮素受体在光诱导性视网膜变性中的作用

Endothelin-1 and endothelin receptors in light-induced retinal degeneration.

作者信息

Torbidoni Vanesa, Iribarne María, Ogawa Liliana, Prasanna Ganesh, Suburo Angela M

机构信息

Facultad de Ciencias Biomédicas, Universidad Austral, Pilar, Buenos Aires B1629AHJ, Argentina.

出版信息

Exp Eye Res. 2005 Sep;81(3):265-75. doi: 10.1016/j.exer.2004.12.024.

DOI:10.1016/j.exer.2004.12.024
PMID:16129094
Abstract

We have studied the distribution of endothelinergic molecules: prepro-endothelin-1 (PPET-1), endothelin-1 (ET-1), and receptors A and B (ET-A) and (ET-B) in the retina of mice. The localization of these molecules in normal mice was compared to their localization in retinas from animals submitted to continuous illumination during 1, 6, 9 or 18 days. We also evaluated the distribution of smooth muscle actin (SMA) and glial markers, glial fibrillary acidic protein (GFAP) and glutamine synthase (GS). PPET-1 immunoreactivity mainly appeared in retinal pigment epithelium (RPE) and cells of the ganglion cell layer (GCL), whereas ET-1 immunoreactivity was present in the RPE, outer plexiform layer (OPL) and astrocytes. Astrocytes exhibited the strongest immunostaining in the retina. ET-A immunoreactivity was observed in endothelium, RPE, OPL and cells of the GCL. By contrast, ET-B immunoreactivity could be detected in endothelial cells, horizontal cells and astrocytes. Astrocytes of the optic nerve also exhibited ET-1, ET-A, and ET-B immunoreactivities. After light-induced degeneration, there was an increase of RPE immunostaining. Degeneration of photoreceptors was accompanied by disappearance of immunoreactivity in the OPL. However, ET-A immunoreactivity appeared in the amacrine sublayer of the INL. There was an enormous increase in astrocytes and its cell processes. The increase of astrocytic immunoreactivities for ET-1 and ET-B was confirmed by quantitative image analysis. Growth of astrocytic cell processes was most marked around retinal blood vessels. Our findings indicate that there are at least three endothelinergic pathways in the normal retina: (1) between the RPE and choriocapillaris, (2) at the OPL, and (3) between blood vessels, astrocytes and cells of the GCL. After light-induced degeneration of photoreceptors, endothelinergic molecules were overexpressed at the RPE and astrocytes, but mostly disappeared from the OPL.

摘要

我们研究了内皮素相关分子

前内皮素原-1(PPET-1)、内皮素-1(ET-1)以及A和B型受体(ET-A和ET-B)在小鼠视网膜中的分布。将这些分子在正常小鼠中的定位与在连续光照1、6、9或18天的动物视网膜中的定位进行了比较。我们还评估了平滑肌肌动蛋白(SMA)以及神经胶质标志物胶质纤维酸性蛋白(GFAP)和谷氨酰胺合成酶(GS)的分布。PPET-1免疫反应主要出现在视网膜色素上皮(RPE)和神经节细胞层(GCL)的细胞中,而ET-1免疫反应则存在于RPE、外网状层(OPL)和星形胶质细胞中。星形胶质细胞在视网膜中表现出最强的免疫染色。在血管内皮、RPE、OPL和GCL的细胞中观察到ET-A免疫反应。相比之下,在血管内皮细胞、水平细胞和星形胶质细胞中可检测到ET-B免疫反应。视神经的星形胶质细胞也表现出ET-1、ET-A和ET-B免疫反应。光诱导变性后,RPE免疫染色增加。光感受器变性伴随着OPL中免疫反应的消失。然而,ET-A免疫反应出现在内核层(INL)的无长突细胞亚层。星形胶质细胞及其细胞突起大量增加。通过定量图像分析证实了星形胶质细胞对ET-1和ET-B免疫反应的增加。星形胶质细胞突起的生长在视网膜血管周围最为明显。我们的研究结果表明,正常视网膜中至少存在三条内皮素能通路:(1)RPE与脉络膜毛细血管之间;(2)在OPL处;(3)血管、星形胶质细胞与GCL的细胞之间。光诱导光感受器变性后,内皮素相关分子在RPE和星形胶质细胞中过度表达,但大多从OPL消失。

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