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. 2023 Feb 24;12(5):737.
doi: 10.3390/cells12050737.

Twenty Novel MicroRNAs in the Aqueous Humor of Pseudoexfoliation Glaucoma Patients

Marcin Czop  1 , Karolina Gasińska  2 , Ewa Kosior-Jarecka  2 , Dominika Wróbel-Dudzińska  2 , Janusz Kocki  1 , Tomasz Żarnowski  2
Affiliations

Twenty Novel MicroRNAs in the Aqueous Humor of Pseudoexfoliation Glaucoma Patients

Marcin Czop et al. Cells. .

Abstract

The microRNAs (miRNAs) are short non-coding RNAs (19-25 nt) that regulate the level of gene expression at the post-transcriptional stage. Altered miRNAs expression can lead to the development of various diseases, e.g., pseudoexfoliation glaucoma (PEXG). In this study, we assessed the levels of miRNA expression in the aqueous humor of PEXG patients using the expression microarray method. Twenty new miRNA molecules have been selected as having the potential to be associated with the development or progression of PEXG. Ten miRNAs were downregulated in PEXG (hsa-miR-95-5p, hsa-miR-515-3p, hsa-mir-802, hsa-miR-1205, hsa-miR-3660, hsa-mir-3683, hsa -mir-3936, hsa-miR-4774-5p, hsa-miR-6509-3p, hsa-miR-7843-3p) and ten miRNAs were upregulated in PEXG (hsa-miR-202 -3p, hsa-miR-3622a-3p, hsa-mir-4329, hsa-miR-4524a-3p, hsa-miR-4655-5p, hsa-mir-6071, hsa-mir-6723-5p, hsa-miR-6847-5p, hsa-miR-8074, and hsa-miR-8083). Functional analysis and enrichment analysis showed that the mechanisms that can be regulated by these miRNAs are: extracellular matrix (ECM) imbalance, cell apoptosis (possibly retinal ganglion cells (RGCs)), autophagy, and elevated calcium cation levels. Nevertheless, the exact molecular basis of PEXG is unknown and further research is required on this topic.

Keywords: PEX; PEXG; aqueous humor; glaucoma; miRNA; pseudoexfoliation glaucoma; pseudoexfoliation syndrome.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Lower miRNA expression in the PEXG group compared to the cataract group. Data are shown as mean [log2].
Figure 2
Figure 2
Higher miRNA expression in the PEXG group compared to the cataract group. Data are shown as mean [log2].
Figure 3
Figure 3
Functional network performed using selected downregulated miRNAs in PEXG. The network is made up of the 10 most statistically significant for each miRNA. Analysis made using DIANA-miRPath v3.0.
Figure 4
Figure 4
Functional network performed using selected upregulated miRNAs in PEXG. The network is made up of the 10 most statistically significant for each miRNA. Analysis made using DIANA-miRPath v3.0.
Figure 5
Figure 5
Top 10 terms of the Gene Ontology (GO): Biological Processing (GO:BP), GO: Cellular Compartment (GO:CC), Molecular Function (GO:MF), REACTOME and KEGG (Kyoto Encyclopedia of Genes and Genomes) categories, revealed for glaucoma- and/or pseudoexfoliation syndrome (PEX)-associated genes targeted by downregulated miRNAs found in the current study in the aqueous humor (AH) of patients with PEXG and age-matched controls. p-value—EASE score for enrichment adjusted by the Benjamini correction for multiple-hypothesis testing. The number in brackets following the names of terms indicates the number of associated genes. The plot was generated using the ggplot2 3.3.0 package in the R environment.
Figure 6
Figure 6
Top 10 terms of the Gene Ontology (GO): Biological Processing (GO:BP), GO: Cellular Compartment (GO:CC), Molecular Function (GO:MF), REACTOME, and KEGG (Kyoto Encyclopedia of Genes and Genomes) categories, revealed for glaucoma- and/or pseudoexfoliation syndrome (PEX)-associated genes targeted by upregulated miRNAs found in the current study in the aqueous humor (AH) of patients with PEXG and age-matched controls. p-value—EASE score for enrichment adjusted by the Benjamini correction for multiple-hypothesis testing. The number in brackets following the names of terms indicates the number of associated genes. The plot was generated using the ggplot2 3.3.0 package in an R environment.
Figure 7
Figure 7
Results of protein–protein interaction analysis. The 6 top-scored clusters separated from the PPI network of the genes regulated by downregulated miRNAs found in the current study. The PPI hub gene module (g).
Figure 8
Figure 8
Results of protein–protein interaction analysis. The six top-scored clusters separated from PPI network of the genes regulated by upregulated miRNAs found in the current study.
Figure 9
Figure 9
The PPI hub gene modules from PPI networks of the genes regulated by downregulated (Hub I) and upregulated miRNAs (Hubs IIa, IIb).
See this image and copyright information in PMC

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