Multi-omics analysis unveils the role of lipid metabolism-derived acylation modifications in POAG and its potential implications.
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 e...
| Published in: | Therapeutic Advances in Ophthalmology Vol. 17; pp. 1 - 21 |
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| Main Authors: | , , , , |
| Format: | pictorial research tables/charts Journal Article |
| Published: |
Sage Publications Inc.
12/16/2025
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=190387934&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 190387934 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 25158414 LAW0 jtl: Therapeutic Advances in Ophthalmology issn: 25158414 maglogo: Y pubinfo: dt: 12/16/2025 vid: 17 pid: 344 pub: Sage Publications Inc. place: Thousand Oaks, California artinfo: ui: 190387934 190387934 190387934 10.1177/25158414251405373 190387934 ppf: 1 ppct: 20 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Multi-omics analysis unveils the role of lipid metabolism-derived acylation modifications in POAG and its potential implications. aug: au: Zhao, Sijie Xu, Che Dai, Qing Gao, Ziqing Chen, Jian affil: Conceptualization, Jinan University Faculty of Medical Science, Guangzhou, Guangdong Province, China sug: subj: Lipids Metabolism Multiomics Glaucoma Physiopathology Glaucoma Familial and Genetic Glaucoma Risk Factors Risk Assessment Bioinformatics Proteins Metabolism Intraocular Pressure Anterior Eye Segment Pathology Fibrosis Genetics Human Funding Source Male Female Extracellular Matrix Genomics Proteomics RNA Sequence Analysis Gene Expression Obesity Familial and Genetic Genes Hyperlipidemia Transcription Factors Body Mass Index Biological Markers Blood Analytic Research Case Control Studies Glaucoma Metabolism Conceptual Framework Molecular Docking Simulation Machine Learning Gene Expression Profiling Anterior Eye Segment Metabolism Mendelian Randomization Cytological Techniques Phospholipases Esterases Male Female ab: 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. Plain language summary: Computer analysis reveals how fat metabolism can lead to glaucoma through tiny changes in proteins, pointing to new treatments Glaucoma is a common eye disease that can cause irreversible blindness, often linked to high pressure inside the eye. We know that the way the body processes fat (fat metabolism) plays a role in this disease, but the exact details have been a mystery. Understanding this process is key to finding new ways to treat patients. In our study, we used powerful computer techniques to analyze large amounts of genetic data from the eye tissue of glaucoma patients and healthy individuals. We focused on tiny chemical changes to proteins, which are triggered by fat metabolism. We discovered that four specific fat-related changes were much more common in people with glaucoma. Our analysis also identified two key genes, ALAS2 and PLCE1, that appear to be central to this process. The ALAS2 gene helps produce the chemical building blocks that cause these protein changes. The PLCE1 gene is involved in creating scar tissue in the eye’s drainage system (the trabecular meshwork). This scarring can block fluid from leaving the eye, causing pressure to build up and damaging the optic nerve. These findings provide a new explanation for how problems with fat metabolism can lead to glaucoma. By pinpointing these specific genes and their actions, we have identified promising targets for developing new therapies. Future research could focus on creating drugs that influence these genes or the protein changes they control, potentially preventing scarring and protecting vision. While our results are from computer analysis, they provide a crucial roadmap for the next steps: laboratory experiments to confirm these mechanisms and explore new treatments. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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