Zhang Junyu, Zhou Yu
Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 611731, China.
International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
J Ophthalmol. 2020 Aug 21;2020:2714746. doi: 10.1155/2020/2714746. eCollection 2020.
Age-related macular degeneration (AMD) is the leading cause of severe, permanent vision loss among the elderly in the developed world. The cellular and molecular pathogenesis of initiation and development of AMD remain poorly delineated. The limited resources of the human AMD RPE/choroid tissues impeded the extensive study of the disease. To better understand the molecular and pathway changes in human AMD RPE/choroid tissues, we searched the literature and found three independent studies using high-throughput technology to analyze gene expression in 54 human AMD RPE/choroid tissues and 46 age-matched healthy controls. We downloaded these data, pooled them together, and reanalyzed the difference between molecular and pathways by the Ingenuity Pathway Analysis (IPA) database. Totally, 353 differentially expressed genes (DEGs) were identified, among which 181 genes were downregulated and 172 genes were upregulated in RPE/choroid of AMD patients. Furthermore, several significantly enriched biological processes, including cancer, organismal injury and abnormalities, and ophthalmic disease, were identified associated with these DEGs. By analysis of canonical pathway, the phototransduction pathway and atherosclerosis signaling were the top two significant canonical pathways altered in RPE/choroid tissues in human AMD. As expected, several ophthalmic disease-related molecules, including RHO, PDE6A, 3',5'-cyclic-GMP phosphodiesterase, and G protein alpha, were in the central nodes of disease network. The bioinformatics technology combined with the existing high-throughput data was applied to evaluate the underlying key genes and pathways in human AMD tissues, which may predict downstream and upstream biological processes and identify potential therapeutic intervention targets in human AMD.
年龄相关性黄斑变性（AMD）是发达国家老年人严重永久性视力丧失的主要原因。AMD起始和发展的细胞及分子发病机制仍不清楚。人类AMD视网膜色素上皮（RPE）/脉络膜组织资源有限，阻碍了对该疾病的广泛研究。为了更好地了解人类AMD RPE/脉络膜组织中的分子和信号通路变化，我们检索了文献，发现三项独立研究使用高通量技术分析了54例人类AMD RPE/脉络膜组织和46例年龄匹配的健康对照中的基因表达。我们下载了这些数据，将它们汇总在一起，并通过Ingenuity Pathway Analysis（IPA）数据库重新分析了分子和信号通路之间的差异。总共鉴定出353个差异表达基因（DEG），其中181个基因在AMD患者的RPE/脉络膜中下调，172个基因上调。此外，还确定了几个显著富集的生物学过程，包括癌症、机体损伤和异常以及眼科疾病，这些都与这些DEG相关。通过对经典信号通路的分析，光转导通路和动脉粥样硬化信号通路是人类AMD患者RPE/脉络膜组织中改变最显著的前两条经典信号通路。正如预期的那样，几个与眼科疾病相关的分子，包括视紫红质（RHO）、磷酸二酯酶6A（PDE6A）、3',5'-环磷酸鸟苷磷酸二酯酶和G蛋白α，处于疾病网络的中心节点。将生物信息学技术与现有的高通量数据相结合，用于评估人类AMD组织中的潜在关键基因和信号通路，这可能预测上下游生物学过程，并确定人类AMD的潜在治疗干预靶点。
