The transcriptome of peripheral blood mononuclear cells in patients with clinical subtypes of late age-related macular d
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RESEARCH
Open Access
The transcriptome of peripheral blood mononuclear cells in patients with clinical subtypes of late age-related macular degeneration Yousif Subhi1* , Marie Krogh Nielsen1, Christopher Rue Molbech1,2, Charlotte Liisborg1,2, Helle Bach Søndergaard3, Finn Sellebjerg1,3 and Torben Lykke Sørensen1,2
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. Keywords: Age-related macular degeneration, Choroidal neovascularization, Geographic atrophy, Polypoidal choroidal vasculopathy, Subretinal fibrosis, Peripheral blood mononuclear cells, Transcriptome
Background Age-related macular degeneration (AMD) is the most frequent cause of visual impairment in the developed countries and the demographic developments towards an aging population are expected to continually and significantly increase the disease burden in the years to come [1–3]. Early stages of the disease are characterized by drusen formation. Drusen are deposits of extracellular material and lipoproteins under the retinal pigment * Correspondence: [email protected] 1 Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital, Vestermarksvej 23, DK-4000 Roskilde, Denmark Full list of author information is available at the end of the article
epithelium (RPE) that to a certain extent are considered a normal aging phenomenon, and they are typically asymptomatic [4, 5]. While this stage characterizes the majority of individuals with AMD, an important group of patients experience progression of disease to the late form of AMD [4]. Late AMD manifests with different clinical features. In geographic a
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