Abstract
BackgroundAge-related macular degeneration (AMD) is the leading cause of irreversible blindness in older individuals. Our study aims to identify the key genes and upstream regulators in AMD.MethodsTo screen pathogenic genes of AMD, an integrated analysis was performed by using the microarray datasets in AMD derived from the Gene Expression Omnibus (GEO) database. The functional annotation and potential pathways of differentially expressed genes (DEGs) were further discovered by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We constructed the AMD-specific transcriptional regulatory network to find the crucial transcriptional factors (TFs) which target the DEGs in AMD. Quantitative real time polymerase chain reaction (qRT-PCR) was performed to verify the DEGs and TFs obtained by integrated analysis.ResultsFrom two GEO datasets obtained, we identified 1280 DEGs (730 up-regulated and 550 down-regulated genes) between AMD and normal control (NC). After KEGG analysis, steroid biosynthesis is a significantly enriched pathway for DEGs. The expression of 8 genes (TNC, GRP, TRAF6, ADAMTS5, GPX3, FAP, DHCR7 and FDFT1) was detected. Except for TNC and GPX3, the other 6 genes in qRT-PCR played the same pattern with that in our integrated analysis.ConclusionsThe dysregulation of these eight genes may involve with the process of AMD. Two crucial transcription factors (c-rel and myogenin) were concluded to play a role in AMD. Especially, myogenin was associated with AMD by regulating TNC, GRP and FAP. Our finding can contribute to developing new potential biomarkers, revealing the underlying pathogenesis, and further raising new therapeutic targets for AMD.
Highlights
IntroductionOur study aims to identify the key genes and upstream regulators in Age-related macular degeneration (AMD)
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in older individuals
Age is the major risk factor associated with AMD, but beyond that, vascular endothelial growth factor (VEGF), oxidative stress, inflammation, complement system are associated with risk of AMD [7]
Summary
Our study aims to identify the key genes and upstream regulators in AMD. Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in older individuals [1, 2]. Pathological deposits (drusen) between the Bruch’s membrane and retinal pigment epithelium (RPE) are closely associated with early stage AMD [3]. Late AMD can be classified into the dry form and the wet form [4]. Dry AMD is mainly caused by atrophy of RPE. Wet AMD is characterized by choroidal neovascularization (CNV), subretinal haemorrhage, photoreceptor loss, retinal detachment and visual loss [5, 6]. Despite many efforts for AMD research in recent decades, effective treatments remain absent [8, 9]
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