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

Yousif Subhi, Marie Krogh Nielsen, Christopher Rue Molbech, Charlotte Liisborg, Helle Bach Søndergaard, Finn Sellebjerg, Torben Lykke Sørensen

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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.

OriginalsprogEngelsk
Sider (fra-til)20
TidsskriftImmunity and Ageing
Vol/bind16
DOI
StatusUdgivet - 2019

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