Ceruloplasmin upregulation in retina of murine and human glaucomatous eyes.
Ceruloplasmin upregulation in retina of murine and human glaucomatous eyes.
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小鼠和人青光眼眼视网膜中铜蓝蛋白的上调。
DOI：
10.1167/iovs.06-0497
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发表时间：
2007
影响因子：
4.4
通讯作者：
Danias,John
中科院分区：
文献类型：
--
作者：
Stasi,Kalliopi;Nagel,Dalia;Yang,Xiaoyan;Ren,Lizhen;Mittag,Thom;Danias,John
目的。铜蓝蛋白(CP)的表达在局部增加，作为对许多神经退行性疾病的反应。本研究的目的是证实青光眼中CP上调的结果，在青光眼模型中检测这种上调的时间进程，并更好地定位其在视网膜中的表达。从DBA/2和C57BL/6小鼠的视网膜和脑中提取mRNA和蛋白质，进行RT-PCR和免疫印迹分析。此外，来自相同品系的小鼠的眼睛接受了使用CP特异性抗体的免疫组织化学。对患有或不患有青光眼的受试者的眼睛也进行了CP免疫组织化学分析。青光眼DBA/2小鼠视网膜CP mRNA和CP蛋白表达上调。CP的上调大约发生在广泛视网膜神经节细胞(RGC)死亡的时候，并随着年龄的增加而增加，在视网膜到15月龄时增加，但在脑中不增加。在参考的正常小鼠品系(C57BL/6)中没有检测到与年龄相关的CP上调，这可能会在同一时间框架结束时发生显著的非青光眼RGC丢失。在青光眼患者中，大多数眼也可检测到CP上调。CP的上调定位于视网膜内的Müler细胞和内界膜区域。CP在一种常用的青光眼模型(DBA/2小鼠)和大多数人类青光眼中上调。这种上调的时机表明，它可能代表了视网膜对有害刺激或RGC死亡的反应性变化。这种CP上调可能代表了视网膜内的一种保护机制。
purpose. Ceruloplasmin (Cp) expression is increased locally as a response to many neurodegenerative conditions. The purposes of this study were to confirm findings of Cp upregulation in glaucoma, detect the time course of this upregulation in a glaucoma model, and better localize its expression in the retina.methods. mRNA and protein were extracted from the retina and brain of DBA/2 and C57BL/6 mice and were subjected to analysis by RT-PCR and immunoblotting. In addition, eyes from the same mouse strains were subjected to immunohistochemistry using antibodies specific for Cp. Eyes from human subjects with or without glaucoma were also subjected to immunohistochemical analysis for Cp.results. Cp mRNA and Cp protein were upregulated in the retinas of glaucomatous DBA/2 mice. Upregulation of Cp occurred at approximately the time of extensive retinal ganglion cell (RGC) death and increased with increasing age to 15 months in the retinas but not in the brains of these animals. No age-related Cp upregulation was detected in the reference normal mouse strain (C57BL/6), which can develop significant nonglaucomatous RGC loss toward the end of the same time frame. Cp upregulation was also detected in most eyes from the patients with glaucoma. Cp upregulation was localized to the Müller cells within the retinas and in the area of the inner limiting membrane.conclusions. Cp is upregulated in the retina of a commonly used glaucoma model (the DBA/2 mouse) and in most human glaucomatous eyes. The timing of this upregulation suggests that it may represent a reactive change of the retina in response to a noxious stimulus or to RGC death. Such Cp upregulation may represent a protective mechanism within the retina.