Therapeutic Advances in Ophthalmology · Published 2025-05-01 · DOI 10.1177/25158414251405373
Objective: Primary open-angle glaucoma (POAG) is a leading cause of vision loss, with lipid metabolism implicated in its pathogenesis. Our study explores lipid metabolism-derived acylation modifications in POAG using GEO, GWAS, and PubChem databases. Methods: Integrated multi-omics approaches were employed: Mendelian randomization assessed causal relationships between lipid traits and POAG risk; transcriptomic analysis (gene set variation analysis, weighted gene co-expression network analysis) identified key acylation-related genes; machine learning selected feature genes; and single-cell sequencing validated mechanisms in human trabecular meshwork samples. Results: Four lipid metabolism-derived acylations (palmitoylation, myristoylation, succinylation, malonylation) were significantly upregulated in POAG. Core genes 5′-aminolevulinate synthase 2 (ALAS2) and phospholipase C epsilon 1 (PLCE1) were mechanistically linked: ALAS2 catalyzed acyl-CoA accumulation, while myristoylated PLCE1 promoted trabecular fibrosis via collagen type IV alpha 3 chain interaction. External datasets confirmed these findings. Conclusion: Lipid-derived acylations drive POAG through ALAS2-mediated acyl-CoA production and PLCE1-induced fibrosis, revealing novel targets for intervention. Lipid metabolism-derived acylation modifications, particularly succinylation, propionylation, and myristoylation, may play a crucial role in POAG. These findings highlight the potential role of acylation modifications in POAG and offer new insights into POAG’s molecular mechanisms and potential research directions.
Abstract from DOAJ. Public domain (CC0 1.0).
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