小鼠和人类视网膜色素上皮细胞基因表达谱的比较：对年龄相关性黄斑变性的潜在影响
Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration.
作者信息
Bennis Anna, Gorgels Theo G M F, Ten Brink Jacoline B, van der Spek Peter J, Bossers Koen, Heine Vivi M, Bergen Arthur A
机构信息
Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands; The Netherlands Institute for Neuroscience (NIN-KNAW), Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
The Netherlands Institute for Neuroscience (NIN-KNAW), Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; University Eye Clinic Maastricht, Maastricht University Medical Centre+, Maastricht, The Netherlands.
出版信息
PLoS One. 2015 Oct 30;10(10):e0141597. doi: 10.1371/journal.pone.0141597. eCollection 2015.
BACKGROUND
The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to develop new therapeutics. This requires further in-depth knowledge of the similarities and differences between mouse and human RPE.
METHODS
We performed a microarray study to identify and functionally annotate RPE specific gene expression in mouse and human RPE. We used a meticulous method to determine C57BL/6J mouse RPE signature genes, correcting for possible RNA contamination from its adjacent layers: the choroid and the photoreceptors. We compared the signature genes, gene expression profiles and functional annotations of the mouse and human RPE.
RESULTS
We defined sets of mouse (64), human (171) and mouse-human interspecies (22) RPE signature genes. Not unexpectedly, our gene expression analysis and comparative functional annotation suggested that, in general, the mouse and human RPE are very similar. For example, we found similarities for general features, like "organ development" and "disorders related to neurological tissue". However, detailed analysis of the molecular pathways and networks associated with RPE functions, suggested also multiple species-specific differences, some of which may be relevant for the development of AMD. For example, CFHR1, most likely the main complement regulator in AMD pathogenesis was highly expressed in human RPE, but almost absent in mouse RPE. Furthermore, functions assigned to mouse and human RPE expression profiles indicate (patho-) biological differences related to AMD, such as oxidative stress, Bruch's membrane, immune-regulation and outer blood retina barrier.
CONCLUSION
These differences may be important for the development of new therapeutic strategies and translational studies in age-related macular degeneration.
背景
人类视网膜色素上皮（RPE）在年龄相关性黄斑变性（AMD）的发病机制中起重要作用。AMD是全球失明的主要原因。目前尚无有效的治疗方法。在AMD小鼠模型中进行临床前研究对于开发新的治疗方法至关重要。这需要进一步深入了解小鼠和人类RPE之间的异同。
方法
我们进行了一项微阵列研究，以鉴定和功能注释小鼠和人类RPE中RPE特异性基因表达。我们使用一种细致的方法来确定C57BL/6J小鼠RPE特征基因，校正来自其相邻层脉络膜和光感受器可能的RNA污染。我们比较了小鼠和人类RPE的特征基因、基因表达谱和功能注释。
结果
我们定义了小鼠（64个）、人类（171个）和小鼠-人类种间（22个）RPE特征基因集。不出所料，我们的基因表达分析和比较功能注释表明，总体而言，小鼠和人类RPE非常相似。例如，我们发现了一般特征的相似性，如“器官发育”和“与神经组织相关的疾病”。然而，对与RPE功能相关的分子途径和网络的详细分析也表明存在多种物种特异性差异，其中一些可能与AMD的发展相关。例如，CFHR1很可能是AMD发病机制中的主要补体调节因子，在人类RPE中高度表达，但在小鼠RPE中几乎不存在。此外，赋予小鼠和人类RPE表达谱的功能表明与AMD相关的（病理）生物学差异，如氧化应激、布鲁赫膜、免疫调节和外血视网膜屏障。
结论
这些差异可能对年龄相关性黄斑变性新治疗策略的开发和转化研究很重要。
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