Differential macular and peripheral expression of bestrophin in human eyes and its implication for Best disease
Differential macular and peripheral expression of bestrophin in human eyes and its implication for Best disease
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DOI：
10.1167/iovs.06-0868
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发表时间：
2007-07-01
影响因子：
4.4
通讯作者：
Stone, Edwin M.
中科院分区：
文献类型：
--
作者：
Mullins, Robert F.;Kuehn, Markus H.;Stone, Edwin M.
目的.最好的疾病，或卵黄状黄斑变性，是一种常染色体显性形式的黄斑变性，是由基因突变编码雌激素。在临床检查中，贝斯特病的特征是神经感觉视网膜下的隆起病变，类似于蛋黄。贝斯特病的病变主要局限于黄斑，这是视网膜上负责中央视觉的一个小区域。卵黄状物质的性质和这种病变的发展通常限于黄斑的原因是这种疾病的发病机制中两个未解决的问题。采用免疫组化、Western blot和定量PCR方法检测正常人眼组织中bestrophin蛋白和mRNA的表达。对2例临床诊断为Best病的供体进行了视网膜色素上皮细胞超微结构和组织病理学检查。发现来自具有T6 R突变的Best疾病供体的眼睛在中央视网膜瘢痕内具有含有脂质和糖缀合物的沉积物。这些沉积物可能是卵黄状病变的残留物。在一系列的22个未受影响的眼睛bestrophin的免疫组织化学定位显示，在大多数（18/22）情况下，黄斑标记比黄斑外标记更不稳定。采用定量PCR和蛋白质印迹法证实了这一模式。脑啡肽蛋白水平的地形差异可能部分解释了Best病中黄斑病变的倾向。
Purpose. Best disease, or vitelliform macular degeneration, is an autosomal dominant form of macular degeneration that is caused by mutations in the gene encoding bestrophin. On clinical examination, Best disease is characterized by an elevated lesion beneath the neurosensory retina, resembling an egg yolk. The lesions in Best disease are primarily restricted to the macula, a small region of the retina responsible for central vision. The nature of the vitelliform material and the reason the development of such lesions is usually restricted to the macula are two unsolved questions in the pathogenesis of this disorder.Methods. The expression of bestrophin protein and mRNA was evaluated by immunohistochemistry, Western blot, and quantitative PCR in a series of normal human eyes. The ultrastructure of the retinal pigment epithelium and the histopathology of two donors with clinically diagnosed Best disease were also examined.Results. An eye from a Best disease donor with a T6R mutation was found to have deposits containing lipid and glycoconjugates within the central retinal scar. These deposits may be remnants of the vitelliform lesion. Immunohistochemical localization of bestrophin in a series of 22 unaffected eyes revealed a pattern in which macular labeling was less robust than labeling outside the macula in most (18/22) cases. This pattern was confirmed using quantitative PCR and Western blotting.Conclusions. Topographic differences in the levels of bestrophin protein may in part explain the propensity for the macula to develop lesions in Best disease.