4.5 Article

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

Journal

IMMUNITY & AGEING
Volume 16, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12979-019-0160-0

Keywords

Age-related macular degeneration; Choroidal neovascularization; Geographic atrophy; Polypoidal choroidal vasculopathy; Subretinal fibrosis; Peripheral blood mononuclear cells; Transcriptome

Funding

  1. Danish Eye Research Foundation
  2. Fight for Sight Denmark
  3. Velux Foundation
  4. University of Copenhagen
  5. Bayer AG

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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.

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