Alterations in N6-Methyladenosine (mA) Modification of mRNA in the Sclera of Form-Deprived Myopic Guinea Pig.

Abstract

PURPOSE: This study aimed to provide direct evidence of the potential role of N6-methyladenosine (mA) modification in the progression of myopia. We focused on identifying genes that may be involved in scleral remodeling through mA regulation in myopia. METHODS: We utilized mA methylation immunoprecipitation sequencing (MeRIP-seq) alongside RNA sequencing (RNA-seq) to investigate the levels of mA modification and mRNA expression in the scleras of form-deprived myopic (FDM) guinea pigs. Subsequent bioinformatics analysis was performed to identify the enriched pathways and genes associated with mA modification. RESULTS: Bioinformatic analyses indicated that hypermethylated mRNAs were predominantly associated with the calcium signaling pathway and may participate in extracellular matrix (ECM) remodeling. Through integrated analysis of MeRIP-seq and RNA-seq data, it was found that more than half of the differentially expressed modified genes (DEGs) exhibiting increased mRNA levels also showed an upregulation of mA modification levels. These genes may play significant roles in the process of myopic scleral remodeling in response to elevated levels of methyltransferase METTL14. CONCLUSION: This study highlights the role of mA methylation, mediated by METTL14, in the regulating of key genes involved in calcium signaling and ECM remodeling during myopia progression. These findings suggest that targeting mA modifications may could offer new therapeutic strategies for the treatment of myopia.