Role of N6-methyladenosine-related lncRnas in pseudoexfoliation glaucoma

ABSTRACT

To explore the role of lncRNA m⁶A methylation modification in aqueous humour (AH) of patients with pseudoexfoliation glaucoma (PXG). Patients with open-angle PXG under surgery from June 2021 to December 2021 were selected. Age- and gender-matched patients with age-related cataract (ARC) were chosen as control. Patients underwent detailed ophthalmic examinations. 0.05–0.1 ml AH were extracted during surgery for MeRIP-Seq and RNA-Seq. Joint analysis was used to screen lncRNAs with differential m⁶A methylation modification and expression. Online software tools were used to draw lncRNA-miRNA-mRNA network (ceRNA). Expression of lncRNAs and mRNAs was confirmed using quantitative real-time PCR. A total of 4151 lncRNAs and 4386 associated m⁶A methylation modified peaks were identified in the PXG group. Similarly, 2490 lncRNAs and 2595 associated m⁶A methylation modified peaks were detected in the control. Compared to the ARC group, the PXG group had 234 hypermethylated and 402 hypomethylated m⁶A peaks, with statistically significant differences (| Fold Change (FC) |≥2, p < 0.05). Bioinformatic analysis revealed that these differentially methylated lncRNA enriched in extracellular matrix formation, tight adhesion, TGF- β signalling pathway, AMPK signalling pathway, and MAPK signalling pathway. Joint analysis identified 10 lncRNAs with differential m⁶A methylation and expression simultaneously. Among them, the expression of ENST000000485383 and ROCK1 were confirmed downregulated in the PXG group by RT-qPCR. m⁶A methylation modification may affect the expression of lncRNA and participate in the pathogenesis of PXG through the ceRNA network. ENST000000485383-hsa miR592-ROCK1 May be a potential target pathway for further investigation in PXG m⁶A methylation.

KEYWORDS:

• Pseudoexfoliation glaucoma
• methylation
• aqueous humour
• lncRNA

Disclosure statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Data availability statement

Data are available at reasonable request to the corresponding authors.

Additional information

Funding

This work was supported by the National Key R&D Project of China (2020YFA0112701), the National Natural Science Foundation of China (82171057), the Science and Technology Program of Guangzhou, China (202206080005) Guangdong Provincial Medical Science and Technology Research Fund (A2022301), and Kashi Regional Science and Technology Project (KS2021048). The funding bodies had no role in the design of the study; nor in the collection, analysis, or interpretation of the data; nor in writing the manuscript.