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The Interplay Between Systemic Inflammatory Factors and MicroRNAs in Age-Related Macular Degeneration
Zofia Litwińska1, Anna Sobuś1, Karolina Łuczkowska1
1Department of General Pathology, 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.
Insights
This study reveals distinct patterns of inflammatory factors and microRNAs (miRNAs) in wet and dry age-related macular degeneration (AMD). These findings suggest a complex interplay of intra- and extracellular mechanisms driving AMD pathogenesis.
Area of Science:
- Ophthalmology
- Immunology
- Genetics
Background:
- Age-related macular degeneration (AMD) is a leading cause of vision loss.
- Inflammation is implicated in AMD pathogenesis, involving both systemic factors and intracellular signaling.
- MicroRNAs (miRNAs) are key regulators of inflammatory pathways.
Purpose of the Study:
- To investigate the expression of systemic inflammatory factors and specific miRNAs in patients with wet and dry AMD.
- To explore the association of these factors and miRNAs with AMD subtypes and visual acuity.
Main Methods:
- Analyzed plasma samples from 179 wet AMD, 175 dry AMD, and 121 control patients for soluble inflammatory factors using Luminex technology.
- Assessed miRNA expression in peripheral blood cells (PBNCs) using real-time qPCR.
- Utilized multivariate analysis to identify independent factors associated with AMD.
Main Results:
- Wet AMD showed associations with higher IL-6, GM-CSF, IFN-γ, and specific miRNAs (e.g., miRNA-23a-3p, miRNA-30b), and lower IL-1β, IL-5, IL-10, IL-12, and other miRNAs.
- Dry AMD was linked to higher GM-CSF, IL-6, and different miRNAs (e.g., miRNA-23a-3p, miRNA-126-3p), and lower TNF-α, IL-1β, IL-2, IL-5, IL-10, IL-12, and other miRNAs.
- Correlations between visual acuity and specific inflammatory markers and miRNAs were observed in AMD patients but not controls.
Conclusions:
- Distinct systemic inflammatory profiles and miRNA expression patterns differentiate wet and dry AMD.
- These findings highlight the involvement of both extracellular inflammatory factors and intracellular miRNA regulation in AMD.
- The study suggests a complex, multifactorial inflammatory basis for AMD pathogenesis.
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