Novel retinal and cone photoreceptor transcripts revealed by human macular expression profiling
Novel retinal and cone photoreceptor transcripts revealed by human macular expression profiling
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DOI：
10.1167/iovs.07-0355
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发表时间：
2007-12-01
影响因子：
4.4
通讯作者：
Webster, Andrew R.
中科院分区：
文献类型：
--
作者：
Hornan, Daniel M.;Peirson, Stuart N.;Webster, Andrew R.
目的。黄斑对于视力来说是必不可少的。它比周边视网膜含有更多的视锥感光细胞。在这项研究中，黄斑和富含视杆的周边视网膜中的基因表达进行了比较。方法：使用来自人供眼的2毫米黄斑中心凹和4毫米黄斑穿孔，以及视网膜中央周围的切片，来研究差异基因的表达。多个基因芯片实验结合定量聚合酶链式反应和生物信息学分析。在本研究中，我们检测了已知和以前未知的视网膜基因的表达。结果：发现了几个黄斑丰富的转录本。核孔复合体相互作用蛋白(NPIP)和真核细胞翻译起始因子2α激酶(GCN2)在黄斑中的表达水平接近红/绿视锥视蛋白。利用这些表达分析突出显示的几个基因的蛋白质产物也定位于视网膜。在视锥感光细胞外节中检测到NPIP和组蛋白脱乙酰酶9(HDAC9)蛋白。结论：鉴定黄斑丰富的转录本是了解视网膜视力的分子基础的重要踏脚石。该方法还为影响黄斑和中心凹的疾病提供了极好的候选方案，如年龄相关性黄斑变性(AMD)。事实上，这些转录本中的几个，如NPIP和GCN2，具有与AMD候选基因一致的基因组位置。
PURPOSE. The macula is essential for visual acuity. It contains many more cone photoreceptors than does the peripheral retina. In this study, macular gene expression was compared with that in the rod-rich peripheral retina.METHODS. Two-millimeter foveomacular and four-millimeter macular punches from human donor eyes, in addition to sections of midperipheral retina, were used to study differential gene expression. Multiple microarray experiments were combined with quantitative PCR and bioinformatic analyses. In the present study, the expression of both known and previously unidentified retinal genes was determined.RESULTS. Several macula enriched transcripts were revealed. Nuclear pore complex interacting protein (NPIP) and eukaryotic translation initiation factor 2 alpha kinase (GCN2) were expressed at levels approaching that of red/green cone opsin in the macula. The protein products of several genes highlighted using these expression analyses were also localized in the retina. Both NPIP and histone deacetylase 9 (HDAC9) proteins were detected in cone photoreceptor outer segments.CONCLUSIONS. Characterizing macula enriched transcripts is an important stepping-stone in understanding the molecular basis for visual acuity in the retina. The approach also provides excellent candidates for diseases that affect the macula and fovea such as age-related macular degeneration (AMD). Indeed, several of these transcripts, such as NPIP and GCN2, have genomic loci that are consistent with being candidate genes for AMD.