TY - JOUR
T1 - The transcriptome of peripheral blood mononuclear cells in patients with clinical subtypes of late age-related macular degeneration
AU - Subhi, Yousif
AU - Nielsen, Marie Krogh
AU - Molbech, Christopher Rue
AU - Liisborg, Charlotte
AU - Søndergaard, Helle Bach
AU - Sellebjerg, Finn
AU - Sørensen, Torben Lykke
PY - 2019
Y1 - 2019
N2 - Background: Peripheral blood mononuclear cells (PBMCs) are implicated in the pathogenesis of age-related macular degeneration (AMD). We here mapped the global gene transcriptome of PBMCs from patients with different clinical subtypes of late AMD.Results: We sampled fresh venous blood from patients with geographic atrophy (GA) secondary to AMD without choroidal neovascularizations (n?=?19), patients with neovascular AMD without GA (n?=?38), patients with polypoidal choroidal vasculopathy (PCV) (n?=?19), and aged control individuals with healthy retinae (n?=?20). We isolated PBMCs, extracted RNA, and used microarray to investigate gene expression. Volcano plots identified statistically significant differentially expressed genes (P?<?0.05) at a high magnitude (?30% higher/lower) for GA (62 genes), neovascular AMD (41 genes), and PCV (41 genes). These clinical subtypes differed substantially across gene expression and the following pathways identified in enrichment analyses. In a subgroup analysis, we investigated presence vs. absence of subretinal fibrosis and found 826 differentially expressed genes (?30% higher/lower, P?<?0.05) with relation to mRNA splicing, endothelial migration, and interleukin-1 signaling.Conclusions: We here map the global gene transcriptome of PBMCs related to clinical subtypes of late AMD and find evidence of subtype-specific immunological involvement. Our findings provide a transcriptomic insight into the systemic immunity associated with AMD.
AB - Background: Peripheral blood mononuclear cells (PBMCs) are implicated in the pathogenesis of age-related macular degeneration (AMD). We here mapped the global gene transcriptome of PBMCs from patients with different clinical subtypes of late AMD.Results: We sampled fresh venous blood from patients with geographic atrophy (GA) secondary to AMD without choroidal neovascularizations (n?=?19), patients with neovascular AMD without GA (n?=?38), patients with polypoidal choroidal vasculopathy (PCV) (n?=?19), and aged control individuals with healthy retinae (n?=?20). We isolated PBMCs, extracted RNA, and used microarray to investigate gene expression. Volcano plots identified statistically significant differentially expressed genes (P?<?0.05) at a high magnitude (?30% higher/lower) for GA (62 genes), neovascular AMD (41 genes), and PCV (41 genes). These clinical subtypes differed substantially across gene expression and the following pathways identified in enrichment analyses. In a subgroup analysis, we investigated presence vs. absence of subretinal fibrosis and found 826 differentially expressed genes (?30% higher/lower, P?<?0.05) with relation to mRNA splicing, endothelial migration, and interleukin-1 signaling.Conclusions: We here map the global gene transcriptome of PBMCs related to clinical subtypes of late AMD and find evidence of subtype-specific immunological involvement. Our findings provide a transcriptomic insight into the systemic immunity associated with AMD.
KW - Age-related macular degeneration
KW - Choroidal neovascularization
KW - Geographic atrophy
KW - Polypoidal choroidal vasculopathy
KW - Subretinal fibrosis
KW - Peripheral blood mononuclear cells
KW - Transcriptome
U2 - 10.1186/s12979-019-0160-0
DO - 10.1186/s12979-019-0160-0
M3 - Article
C2 - 31428180
SN - 1742-4933
VL - 16
SP - 20
JO - Immunity and Ageing
JF - Immunity and Ageing
ER -