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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Aging Neurosci. | doi: 10.3389/fnagi.2019.00286

The interplay between systemic inflammatory factors and microRNAs in age-related macular degeneration

 Zofia Litwinska1, Anna Sobus1, Karolina Luczkowska1, Aleksandra Grabowicz2, Katarzyna Mozolewska-Piotrowska2, Krzysztof Safranow3, Milosz P. Kawa1, Boguslaw Machalinski1 and Anna Machalinska2*
  • 1Department of General Pathology, Pomeranian Medical University, Poland
  • 2First Department of Ophthalmology, Pomeranian Medical University, Poland
  • 3Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Poland

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: Macular Degeneration, miRNA, Cytokines, interleukin, Inflammation

Received: 28 Jun 2019; Accepted: 04 Oct 2019.

Copyright: © 2019 Litwinska, Sobus, Luczkowska, Grabowicz, Mozolewska-Piotrowska, Safranow, Kawa, Machalinski and Machalinska. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Anna Machalinska, Pomeranian Medical University, First Department of Ophthalmology, Szczecin, 70-204, West Pomeranian, Poland, annam@pum.edu.pl