The Interplay Between Systemic Inflammatory Factors and MicroRNAs in Age-Related Macular Degeneration

Zofia Litwińska; Anna Sobuś; Karolina Łuczkowska; Aleksandra Grabowicz; Katarzyna Mozolewska-Piotrowska; Krzysztof Safranow; Miłosz Piotr Kawa; Bogusław Machaliński; Anna Machalińska

doi:10.3389/fnagi.2019.00286

The Interplay Between Systemic Inflammatory Factors and MicroRNAs in Age-Related Macular Degeneration

Front Aging Neurosci. 2019 Oct 22:11:286. doi: 10.3389/fnagi.2019.00286. eCollection 2019.

Authors

Zofia Litwińska¹, Anna Sobuś¹, Karolina Łuczkowska¹, Aleksandra Grabowicz², Katarzyna Mozolewska-Piotrowska², Krzysztof Safranow³, Miłosz Piotr Kawa¹, Bogusław Machaliński¹, Anna Machalińska²

Affiliations

¹ Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
² First Department of Ophthalmology, Pomeranian Medical University, Szczecin, Poland.
³ Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland.

Abstract

We aimed to explore the expression of systemic inflammatory factors and selected intracellular miRNAs that regulate inflammatory signaling pathways potentially involved in age-related macular degeneration (AMD) pathogenesis. A total of 179 patients with wet AMD, 175 with dry AMD and 121 controls were enrolled in the study. Soluble inflammatory factors were analyzed in plasma samples using Luminex technology. Expression of selected miRNAs was analyzed in isolated nucleated peripheral blood cells (PBNCs) using real-time qPCR. Wet AMD was an independent factor associated with higher concentrations of IL-6 (β = +0.24, p = 0.0004), GM-CSF (β = +0.31, p < 0.001), IFN-γ (β = +0.58, p < 0.001), higher expression of miRNA-23a-3p (β = +0.60, p < 0.0001), miRNA-30b (β = +0.32, p < 0.0001), miRNA-191-5p (β = +0.28, p < 0.0001) and lower concentration of IL-1β (β = -0.25, p = 0.0003), IL-5 (β = -0.45, p < 0.001), IL-10 (β = -0.45, p < 0.001), IL-12 (β = -0.35, p < 0.001), lower expression of miRNA-16-5p (β = -0.31, p < 0.0001), miRNA-17-3p (β = -0.18, p = 0.01), miRNA-150-5p (β = -0.18, p = 0.01) and miRNA-155-5p (β = -0.47, p < 0.0001). Multivariate analysis revealed that dry AMD was an independent factor associated with higher concentration of GM-CSF (β = +0.34, p < 0.001), IL-6 (β = +0.13, p = 0.05), higher expression of miRNA-23a-3p (β = +0.60, p < 0.0001), miRNA-126-3p (β = +0.23, p = 0.0005), miRNA-126-5p (β = +0.16, p = 0.01), miRNA 146a (β = +0.14, p = 0.03), and mRNA191-5p (β = +0.15, p = 0.03) and lower concentrations of TNF-α (β = +0.24, p = 0.0004), IL-1β (β = -0.39, p < 0.001), IL-2 (β = -0.20, p = 0.003), IL-5 (β = -0.54, p < 0.001), IL-10 (β = -0.56, p < 0.001), IL-12 (β = -0.51, p < 0.001), lower expression of miRNA-16-5p (β = -0.23, p = 0.0004), miRNA-17-3p (β = -0.20, p = 0.003) and miRNA-17-5p (β = -0.19, p = 0.004). Negative correlations between visual acuity and WBC, lymphocyte count, TNF-α, IL-1 β, IL-2, IL-4, IL-6, IL-10 concentrations and miRNA-191-5p, as well as positive correlations between visual acuity and miRNA-126-3p, -126-5p, and -155-5p PBNCs expression were found in AMD patients. No such correlations were found in the control group. Our results may suggest the role of both intra- and extracellular mechanisms implicated in inflammatory response regulation in multifactorial AMD pathogenesis.

Keywords: cytokines; inflammation; interleukin; macular degeneration; miRNA.