title: Transcriptome Analysis on Monocytes from Patients with Neovascular Age-Related Macular Degeneration.
abstract: Mononuclear phagocytes (MPs), including monocytes/macrophages, play complex roles in age-related macular degeneration (AMD) pathogenesis. We reported altered gene-expression signature in peripheral blood mononuclear cells from AMD patients, and a chemokine receptor signature on AMD monocytes. To obtain comprehensive understanding of MP involvement, particularly in peripheral circulation in AMD, we performed global gene expression analysis in monocytes. We separated monocytes from treatment-naïve neovascular AMD (nvAMD) patients (n = 14) and age-matched controls (n = 15), and performed microarray and bioinformatics analysis. Quantitative real-time PCR was performed on other sets of nvAMD (n = 25), atrophic AMD (n = 21), and controls (n = 28) for validation. This validated microarray genes (like TMEM176A/B and FOSB) tested, including differences between nvAMD and atrophic AMD. We identified 2,165 differentially-expressed genes (P < 0.05), including 79 genes with log2 fold change ≥1.5 between nvAMD and controls. Functional annotation using DAVID and TANGO demonstrated immune response alterations in AMD monocytes (FDR-P <0.05), validated by randomized data comparison (P < 0.0001). GSEA, ISMARA, and MEME analysis found immune enrichment and specific involved microRNAs. Enrichment of differentially-expressed genes in monocytes was found in retina via SAGE data-mining. These genes were enriched in non-classical vs. classical monocyte subsets (P < 0.05). Therefore, global gene expression analysis in AMD monocytes reveals an altered immune-related signature, further implicating systemic MP activation in AMD.
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Michelle
authors.initials: M
authors.lastname: Grunin
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Shira-
authors.initials: S
authors.lastname: Hagbi-Levi
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Batya
authors.initials: B
authors.lastname: Rinsky
authors.affiliation: Genomic Data Analysis Unit, Hebrew University, Jerusalem, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Smith
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Itay
authors.initials: I
authors.lastname: Chowers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020256:Choroidal Neovascularization / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007962:Leukocytes; D008268:Macular Degeneration / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D010586:Phagocytes / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics*; D012160:Retina / Q000503:physiopathology; D059467:Transcriptome / Q000235:genetics; D057135:Wet Macular Degeneration / Q000097:blood* / Q000235:genetics / Q000503:physiopathology
chemical_list: D019707:Receptors, Chemokine