Identification of Key Genes and Pathways Associated with Age-Related Macular Degeneration

Abstract

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.

Investigation of Key Signaling Pathways Associating miR-204 and Common Retinopathies

“…By knocking down the genes and examining the pathways, they showed that the diagnosis and examination of FADS2 and ACAT2 in the early stages of the disease will help to improve the quality of treatments [ 60 ]. Zhang et al displayed that RHO, PDE6A, 3′,5′-cyclic-GMP phosphodiesterase, and G protein alpha pathways play a role in the development and intensification of AMD [ 61 ]. Also, the study by Su et al, which analyzed this database, eventually nominated hsa_circRNA7329/hsa-miR-9/SCD, where hsa_circRNA7329 is in line with AMD's development [ 62 ].…”

Epigenomic signatures in age-related macular degeneration: Focus on their role as disease modifiers and therapeutic targets

“…All of them clustered into molecular pathways (mainly phototransduction-related mechanisms and inflammatory/immune response) that exacerbate the RPE damage and, thus, are relevant to the etiopathogenesis of AMD. 80,81…”

“…All of them clustered into molecular pathways (mainly phototransduction-related mechanisms and inflammatory/immune response) that exacerbate the RPE damage and, thus, are relevant to the etiopathogenesis of AMD. 80,81 As mentioned throughout the manuscript, epigenetic elements such as DNA methylation changes occur at level of anti-oxidant factors and genes involved in the regulation of proliferation; miRNAs modulate the expression of angiogenic factors; histone modifiers appear dysregulated in disease-relevant genes. 25,26,31,68,69 Such evidence of dysregulation of gene expression may also suggest a potential upstream role for the epigenetic modifications.…”

Hsp90-associated DNA replication checkpoint protein and proteasome-subunit components are involved in the age-related macular degeneration

“…Recently, RHO, PDE6A, 3′,5′-cyclic-GMP phosphodiesterase, and G protein alpha have been identified as AMD-related genes by canonical pathway analysis using the Ingenuity Pathway Analysis database. [ 34 ] We additionally identified HSP90AA1 , PRPF19 , PSMD4 , PSMD8 , PSMA4 , CHEK1 , SF3B5 , CCT7 , PSMB5 , and PSMB6 as the top ten hub genes associated with AMD. Importantly, in both of the analyzed cohorts, these genes were mostly upregulated in AMD RPE samples compared to healthy control samples.…”