Abstract
We report for the first time an integrated transcriptomic analysis of RPE/choroid dysfunction in AMD (mixed stages) based on combining data from publicly available microarray (GSE29801) and RNAseq (GSE135092) datasets aimed at increasing the ability and power of detection of differentially expressed genes and AMD-associated pathways. The analysis approach employed an integrating quantitative method designed to eliminate bias among different transcriptomic studies. The analysis highlighted 764 meta-genes (366 downregulated and 398 upregulated) in macular AMD RPE/choroid and 445 meta-genes (244 downregulated and 201 upregulated) in non-macular AMD RPE/choroid. Of these, 731 genes were newly detected as differentially expressed (DE) genes in macular AMD RPE/choroid and 434 genes in non-macular AMD RPE/choroid compared with controls. Over-representation analysis of KEGG pathways associated with these DE genes mapped revealed two most significantly associated biological processes in macular RPE/choroid in AMD, namely the neuroactive ligand-receptor interaction pathway (represented by 30 DE genes) and the extracellular matrix-receptor interaction signaling pathway (represented by 12 DE genes). Furthermore, protein-protein interaction (PPI) network identified two central hub genes involved in the control of cell proliferation/differentiation processes, HDAC1 and CDK1. Overall, the analysis provided novel insights for broadening the exploration of AMD pathogenesis by extending the number of molecular determinants and functional pathways that underpin AMD-associated RPE/choroid dysfunction.
Keywords:
age-related macular degeneration; extracellular matrix; neuroactive ligand-receptor; neurodegeneration; retinal pigment epithelium; transcriptome.