Ophthalmic Genetics & Visual Function Branch, NIH, Bethesda, MD 20892-2510, USA.
Hum Mol Genet. 2010 Jun 15;19(12):2468-86. doi: 10.1093/hmg/ddq129. Epub 2010 Apr 1.
Retinal pigment epithelium (RPE) is a polarized cell layer critical for photoreceptor function and survival. The unique physiology and relationship to the photoreceptors make the RPE a critical determinant of human vision. Therefore, we performed a global expression profiling of native and cultured human fetal and adult RPE and determined a set of highly expressed 'signature' genes by comparing the observed RPE gene profiles to the Novartis expression database (SymAtlas: http://wombat.gnf.org/index.html) of 78 tissues. Using stringent selection criteria of at least 10-fold higher expression in three distinct preparations, we identified 154 RPE signature genes, which were validated by qRT-PCR analysis in RPE and in an independent set of 11 tissues. Several of the highly expressed signature genes encode proteins involved in visual cycle, melanogenesis and cell adhesion and Gene ontology analysis enabled the assignment of RPE signature genes to epithelial channels and transporters (ClCN4, BEST1, SLCA20) or matrix remodeling (TIMP3, COL8A2). Fifteen RPE signature genes were associated with known ophthalmic diseases, and 25 others were mapped to regions of disease loci. An evaluation of the RPE signature genes in a recently completed AMD genomewide association (GWA) data set revealed that TIMP3, GRAMD3, PITPNA and CHRNA3 signature genes may have potential roles in AMD pathogenesis and deserve further examination. We propose that RPE signature genes are excellent candidates for retinal diseases and for physiological investigations (e.g. dopachrome tautomerase in melanogenesis). The RPE signature gene set should allow the validation of RPE-like cells derived from human embryonic or induced pluripotent stem cells for cell-based therapies of degenerative retinal diseases.
视网膜色素上皮 (RPE) 是一层极化细胞层，对光感受器的功能和存活至关重要。其独特的生理学特性和与光感受器的关系使 RPE 成为人类视觉的关键决定因素。因此，我们对原代和培养的人胎儿和成人 RPE 进行了全局表达谱分析，并通过将观察到的 RPE 基因谱与诺华表达数据库（SymAtlas：http://wombat.gnf.org/index.html）中的 78 种组织进行比较，确定了一组高度表达的“特征”基因。使用至少在三种不同制剂中表达高 10 倍的严格选择标准，我们鉴定了 154 个 RPE 特征基因，并用 qRT-PCR 分析在 RPE 中和在 11 种独立组织中进行了验证。高度表达的特征基因中有几个编码参与视觉循环、黑色素生成和细胞黏附的蛋白质，基因本体论分析使 RPE 特征基因能够分配到上皮通道和转运体（ClCN4、BEST1、SLCA20）或基质重塑（TIMP3、COL8A2）。15 个 RPE 特征基因与已知的眼科疾病相关，另外 25 个基因映射到疾病位点区域。在最近完成的 AMD 全基因组关联 (GWA) 数据集评估中，发现 TIMP3、GRAMD3、PITPNA 和 CHRNA3 特征基因可能在 AMD 发病机制中具有潜在作用，值得进一步研究。我们提出 RPE 特征基因是视网膜疾病和生理研究（例如黑色素生成中的多巴色素互变异构酶）的优秀候选基因。RPE 特征基因集应允许验证源自人胚胎或诱导多能干细胞的 RPE 样细胞，用于退行性视网膜疾病的细胞治疗。
