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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Expression of VEGFA-regulating miRNAs and mortality in wet AMD
Janusz Blasiak1, Cezary Watala2, Raimo Tuuminen3,4
1Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
Abstract:
MicroRNAs (miRNAs) regulate gene expression; many of them act in the retinal pigment epithelium (RPE), and RPE degeneration is known to be a critical factor in age-related macular degeneration (AMD). Repeated injections with anti-VEGFA (vascular endothelial growth factor A) are the only effective therapy in wet AMD. We investigated the correlation between the expression of 18 miRNAs involved in the regulation of the VEGFA gene in serum of 76 wet AMD patients and 70 controls. Efficacy of anti-VEGFA treatment was evaluated by counting the number of injections delivered up to 12 years. In addition, we compared the relative numbers of deaths in patient with AMD and control groups. We observed a decreased expression of miR-34-5p, miR-126-3p, miR-145-5p and miR-205-5p in wet AMD patients as compared with controls. These miRNAs are involved in the regulation of angiogenesis, cytoprotection and protein clearance. No miRNA was significantly correlated with the treatment outcome. Wet AMD patients had greater mortality than controls, and their survival was inversely associated with the number of anti-VEGFA injections per year. No association was observed between miRNA expression and mortality. Our study emphasizes the need to clarify the role of miRNA regulation in AMD pathogenesis.
Insights
This study found lower levels of specific microRNAs (miRNAs) in wet age-related macular degeneration (AMD) patients, but these did not predict treatment response. Wet AMD patients showed higher mortality, linked to treatment frequency, not miRNA levels.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Age-related macular degeneration (AMD) involves retinal pigment epithelium (RPE) degeneration.
- Anti-VEGF (vascular endothelial growth factor) therapy is the primary treatment for wet AMD.
- MicroRNAs (miRNAs) are key regulators of gene expression, including VEGFA.
Purpose of the Study:
- To investigate the correlation between serum miRNA expression and wet AMD.
- To assess the relationship between miRNA expression and anti-VEGF treatment efficacy.
- To compare mortality rates between wet AMD patients and controls.
Main Methods:
- Serum samples from 76 wet AMD patients and 70 controls were analyzed for 18 specific miRNAs.
- Anti-VEGF treatment efficacy was measured by the number of injections over 12 years.
- Mortality data for both groups were compared.
Main Results:
- Decreased expression of miR-34-5p, miR-126-3p, miR-145-5p, and miR-205-5p was observed in wet AMD patients.
- These miRNAs are implicated in angiogenesis, cytoprotection, and protein clearance.
- No significant correlation was found between miRNA expression and treatment outcome or mortality.
Conclusions:
- Specific miRNAs are downregulated in wet AMD patients.
- Wet AMD patients exhibit increased mortality, inversely related to anti-VEGF injection frequency.
- Further research is needed to elucidate the role of miRNA regulation in AMD pathogenesis.

