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补体因子H:在眼中的时空表达与定位

Complement factor H: spatial and temporal expression and localization in the eye.

作者信息

Mandal Md Nawajes A, Ayyagari Radha

机构信息

Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan 48105, USA.

出版信息

Invest Ophthalmol Vis Sci. 2006 Sep;47(9):4091-7. doi: 10.1167/iovs.05-1655.

Abstract

PURPOSE

Complement factor H (CFH) is a component of the mammalian complement system, which regulates the alternative pathway of complement activation and protects the host cell from inappropriate complement activation. CFH is a key regulator of innate immunity, and CFH deficiency leads to membranoproliferative glomerulonephritis type II. A variation in human CFH, Y402H, has been shown to be associated with an increased risk for age-related macular degeneration. The authors describe studies on the spatial and temporal expression of the CFH gene and localization of this protein in ocular tissues to gain insight into its role in the eye.

METHODS

CFH expression in human and mouse tissues was studied by quantitative RT-PCR and Western blot analysis, and localization of CFH was studied by immunohistochemical analysis followed by fluorescence microscopy.

RESULTS

In human and mouse, CFH expression was found to be similar to the highest level of expression in the liver. In ocular tissue, CFH was detected in the distalmost optic nerve (3 mm) cut from the scleral surface of the eyeball, sclera, RPE-choroid, retina, lens, and ciliary body. In mouse, Cfh expression was observed from early embryonic stages, and in the eye its expression increased with age.

CONCLUSIONS

A significant level of CFH expression is maintained in different ocular tissues during development and aging. Sustained high levels of CFH expression in eye tissues suggest that this protein may play a role in protecting these tissues from indiscriminate complement activation and inflammatory insult.

摘要

目的

补体因子H(CFH)是哺乳动物补体系统的一个组成部分,它调节补体激活的替代途径,并保护宿主细胞免受不适当的补体激活。CFH是先天免疫的关键调节因子,CFH缺乏会导致II型膜增生性肾小球肾炎。人类CFH的一种变异体Y402H已被证明与年龄相关性黄斑变性的风险增加有关。作者描述了关于CFH基因的时空表达以及该蛋白在眼组织中的定位的研究,以深入了解其在眼睛中的作用。

方法

通过定量逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹分析研究了人和小鼠组织中CFH的表达,并通过免疫组织化学分析和荧光显微镜检查研究了CFH的定位。

结果

在人和小鼠中,发现CFH的表达与肝脏中的最高表达水平相似。在眼组织中,在从眼球巩膜表面切下的最远端视神经(3毫米)、巩膜、视网膜色素上皮-脉络膜、视网膜、晶状体和睫状体中检测到CFH。在小鼠中,从胚胎早期阶段就观察到Cfh的表达,并且在眼睛中其表达随年龄增加。

结论

在发育和衰老过程中,不同眼组织中维持着显著水平的CFH表达。眼组织中持续高水平的CFH表达表明该蛋白可能在保护这些组织免受无差别补体激活和炎性损伤方面发挥作用。

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