Methylome profiling reveals epigenetic alterations in the trabecular meshwork of primary open-angle glaucoma.
Liu Ke, Xu Wang-Yang, Fu Ruiqing, Wang Yiwen
AI Summary
This study found extensive DNA hypomethylation in glaucoma patients' eye drainage tissue, impacting genes involved in extracellular matrix dysregulation, offering new therapeutic targets.
Abstract
Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide. While aberrant DNA methylation may contribute, a genome-wide profile in trabecular meshwork (TM) is lacking. This study performed reduced-representation bisulfite sequencing (RRBS) on TM samples from 42 POAG patients and 20 non-glaucomatous controls, identifying 8885 significant differentially methylated CpG sites (DMCs) and 3148 differentially methylated regions (DMRs), revealing a pronounced hypomethylation pattern in POAG. Hypomethylated genes were associated with ossification, collagen fibril organization, and the RhoA/ROCK signaling, whereas hypermethylated genes were enriched in androgen receptor signaling, the NABA core matrisome, and actin filament processes-collectively highlighting extracellular matrix (ECM) dysregulation as a central theme. Integrated methylome-transcriptome analysis identified four high-priority genes (COL5A1, COL5A2, JAM3, and HTRA1) among hypomethylated-upregulated candidates, implicating them in pathogenic ECM remodeling in POAG. This study presents the first RRBS-based methylome profile of POAG, revealing significant epigenetic alterations in pathways and genes related to TM dysfunction. These findings enhance our understanding of the molecular mechanisms underlying POAG and may inform future therapeutic strategies.
Key Concepts4
Reduced-representation bisulfite sequencing (RRBS) on trabecular meshwork (TM) samples from 42 primary open-angle glaucoma (POAG) patients and 20 non-glaucomatous controls identified 8885 significant differentially methylated CpG sites (DMCs) and 3148 differentially methylated regions (DMRs) in POAG, revealing a pronounced hypomethylation pattern.
In primary open-angle glaucoma (POAG), hypomethylated genes in trabecular meshwork (TM) samples were associated with ossification, collagen fibril organization, and the RhoA/ROCK signaling pathway.
In primary open-angle glaucoma (POAG), hypermethylated genes in trabecular meshwork (TM) samples were enriched in androgen receptor signaling, the NABA core matrisome, and actin filament processes, collectively highlighting extracellular matrix (ECM) dysregulation as a central theme.
Integrated methylome-transcriptome analysis identified COL5A1, COL5A2, JAM3, and HTRA1 as high-priority genes among hypomethylated-upregulated candidates in the trabecular meshwork of primary open-angle glaucoma (POAG) patients, implicating them in pathogenic extracellular matrix (ECM) remodeling.
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