Differential miRNA Expression: Signature for Glaucoma in Pseudoexfoliation

Area of Science:

• Ophthalmology
• Molecular Biology
• Genetics

Background:

• Pseudoexfoliation (PXF) syndrome is a common cause of secondary glaucoma.
• The molecular mechanisms underlying PXF and its progression to pseudoexfoliation glaucoma (PXG) are not fully understood.

Purpose of the Study:

• To investigate the microRNA (miRNA) profile in patients with different stages of pseudoexfoliation (PXF).
• To explore the role of miRNAs and their downstream targets in the pathogenesis of PXF and PXG.

Main Methods:

• miRNA profiling using polymerase chain reaction (PCR) arrays in peripheral blood of patients with ocular hypertension (OHT) and PXG.
• Validation of identified miRNAs and quantification of serum transforming growth factor-β1 (TGF-β1) by ELISA.
• Analysis of downstream targets of TGF-β1 and unfolded protein response (UPR) genes using RT-qPCR and bioinformatics tools (miRbase, DIANA mirPathv3.1).

Main Results:

• Three miRNAs (hsa-miR-122-5p, hsa-miR-124-3p, hsa-miR-424-5p) were upregulated in PXG, targeting TGF-β1, fibrosis/ECM, and proteoglycan metabolism pathways.
• Unfolded protein response (UPR) genes were downregulated in all PXF stages, suggesting a role in protein aggregate formation.
• Serum TGF-β1 levels increased with disease progression in PXG and were associated with differential expression of fibrotic genes, particularly via the SMAD3 pathway.

Conclusions:

• Circulating miRNAs that differentially regulate TGF-β1 and downstream targets, including UPR genes, are implicated in the pathogenesis of glaucoma in PXF.
• These molecular alterations represent potential key mechanisms driving glaucoma onset in pseudoexfoliation syndrome.