Functional roles of bestrophins in ocular epithelia.
Functional roles of bestrophins in ocular epithelia.
复制标题
DOI：
10.1016/j.preteyeres.2009.04.004
复制
发表时间：
2009-05
影响因子：
17.8
通讯作者：
Peachey, Neal S.
中科院分区：
文献类型：
--
作者：
Marmorstein, Alan D.;Cross, Harold E.;Peachey, Neal S.
关键词：
人类基因组中有四个Bestrophin蛋白质家族成员，其中两个已知在眼睛中表达。编码Bestrophin-1(Best1)蛋白的基因BEST1(前身为VMD2)于1998年首次被发现。该基因的突变现在已经与四种临床上可区分的人类眼病有关，统称为“bestrophinopsis”。在过去的十年里，实验室一直在试图了解Best1突变是如何导致从黄斑变性到纳米眼球的各种眼病的。我们的大部分知识来自于研究，这些研究试图了解Best1突变或功能障碍如何导致这些最常见疾病的经典症状：最佳卵黄样黄斑营养不良(BVMD)。BVMD是一种显性特征，其电生理学特征是眼电波光峰减弱，临床视网膜电信号正常。再加上Best1在视网膜色素上皮(RPE)基底侧质膜上的定位和异源表达研究的数据，导致了Best1产生光峰的假设，并且bestrophins是一个钙激活的氯通道(CaCC)家族。然而，来自Best1基因敲除和敲入小鼠的数据，加上最近发现的一种隐性脑病，表明Best1不会产生光峰。最近发现，Best2在睫状体无色素上皮细胞中有表达。然而，Best2基因敲除小鼠的水动力学不支持Best2作为氯离子通道的作用。因此，我们需要重新评估Bestrophins的CACC功能，以及这一功能的丧失与临床疾病的关系。在这篇文章中，我们检查了从组织类型和动物模型中获得的数据，并讨论了Bestrophin的研究现状，Best1和Best2在眼上皮细胞和眼电生理学中可能扮演的角色，以及这些功能的干扰可能如何导致疾病。
There are four members of the bestrophin family of proteins in the human genome, of which two are known to be expressed in the eye. The gene BEST1 (formerly VMD2) which encodes the protein bestrophin-1 (Best1) was first identified in 1998. Mutations in this gene have now been associated with four clinically distinguishable human eye diseases, collectively referred to as “bestrophinopathies”. Over the last decade, laboratories have sought to understand how Best1 mutations could result in eye diseases that range in presentation from macular degeneration to nanophthalmos. The majority of our knowledge comes from studies that have sought to understand how Best1 mutations or dysfunction could induce the classical symptoms of the most common of these diseases: Best vitelliform macular dystrophy (BVMD). BVMD is a dominant trait that is characterized electrophysiologically by a diminished electrooculogram light peak with a normal clinical electroretinogram. This together with the localization of Best1 to the retinal pigment epithelium (RPE) basolateral plasma membrane and data from heterologous expression studies, have led to the proposal that Best1 generates the light peak, and that bestrophins are a family of Ca2+ activated Cl- channels (CaCCs). However, data from Best1 knock-out and knock-in mice, coupled with the recent discovery of a recessive bestrophinopathy suggest that Best1 does not generate the light peak. Recently Best2 was found to be expressed in non-pigmented epithelia in the ciliary body. However, aqueous dynamics in Best2 knock-out mice do not support a role for Best2 as a Cl- channel. Thus, the purported CaCC function of the bestrophins and how loss of this function relates to clinical disease needs to be reassessed. In this article, we examine data obtained from tissue-type and animal models and discuss the current state of bestrophin research, what roles Best1 and Best2 may play in ocular epithelia and ocular electrophysiology, and how perturbation of these functions may result in disease.
登录
查看更多内容
影响因子：
4.4
作者：
Bakall, Benjamin;McLaughlin, Precious;Marmorstein, Alan D.
通讯作者：
Marmorstein, Alan D.
影响因子：
5.3
作者：
Bakall, B;Marknell, T;Wadelius, C
通讯作者：
Wadelius, C
影响因子：
4.4
作者：
Bakall, B;Marmorstein, LY;Marmorstein, AD
通讯作者：
Marmorstein, AD
影响因子：
64.5
作者：
Burgess, DL;Jones, JM;Noebels, JL
通讯作者：
Noebels, JL
DOI：
10.1136/bjo.46.8.449
发表时间：
1962-08-01
期刊：
The British journal of ophthalmology
影响因子：
--
作者：
Arden, G B;Barrada, A;Kelsey, J H
通讯作者：
Kelsey, J H