The transcriptome of peripheral blood mononuclear cells in patients with clinical subtypes of late age-related macular degeneration

Abstract

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.