Explicating the Role of miR-638 in the Pathogenesis of Exfoliation Syndrome and Exfoliation Glaucoma

Author(s): Alka Khera, Surinder Singh Pandav, Jagat Ram, Faisal Thattaruthody, Parul Chawla Gupta, Gaurav Kumar, Nirbhai Singh, Madhu Khullar

Introduction: Pseudoexfoliation syndrome (XFS) poses a significant risk for pseudoexfoliation glaucoma (XFG) by affecting intraocular pressure (IOP) and visual acuity. Previous studies have linked microRNAs (miRNAs) to the development of XFS and XFG. This research aims to explore the varying levels of miRNAs in the anterior lens capsule (ALC) of individuals with XFS, XFG, and those without the conditions.

Methods: Total RNA, including miRNA, was extracted from the ALC of XFS, XFG and cataract (CAT) patients. A miRNA microarray was performed and significantly expressed miRNAs were confirmed using real-time PCR. Furthermore, the expression levels of miR-638 and its target genes were validated using real-time PCR, and oxidative stress levels were evaluated using a lipid peroxidation (LPO) assay.

Results: Analysis of RNA extracted from ALC samples revealed the presence of 2550 miRNAs, with 44 showing distinct expression patterns among the groups. Further validation through qRT-PCR in 12 samples per group highlighted 8 clinically important miRNAs, with miR-638 significantly upregulated in XFG compared to both XFS and control groups (p > 0.0001). Investigation into potential targets of miR-638 identified SRY-Box transcription factor 2 (SOX2) as a key player, displaying marked downregulation in XFG compared to controls. Additionally, testing for lipid peroxidation function revealed heightened oxidative stress in samples from individuals with XFS and XFG.

Conclusion: These findings collectively suggest that the dysregulation of miR-638, its target gene SOX2, and the disrupted balance between oxidative and antioxidative processes may contribute significantly to the pathophysiology of XFG.