Primary open-angle glaucoma (POAG) is a progressive optic neuropathy that leads to irreversible vision loss, primarily due to dysfunction of the trabecular meshwork (TM). Although impaired autophagy has been implicated in POAG pathogenesis, its molecular drivers remain poorly defined. This study systematically investigated autophagy-related genes (ATGs) in TM tissue from POAG patients. Transcriptomic datasets (GSE4316 and GSE27276) were analyzed to identify differentially expressed genes (DEGs). A curated list of autophagy-related genes (ATGs) from HADb and GeneCards was intersected with DEGs to identify differentially expressed ATGs (DEATGs). Functional analyses included Gene Ontology (GO) and KEGG pathway enrichment, protein-protein interaction (PPI) network construction, hub gene identification, immune cell infiltration profiling via single-sample gene set enrichment analysis (ssGSEA), and molecular docking to evaluate predicted interactions between latanoprost and hub proteins. A total of 990 DEGs were identified, including 15 DEATGs. Among these, S100A8 and S100A9 emerged as hub genes, exhibiting strong functional similarity and central roles within the PPI network. Enrichment analysis revealed significant involvement in autophagy regulation, tyrosine metabolism, and oxidative phosphorylation. Notably, molecular docking predicted high-affinity binding between latanoprost and S100A9. Immune profiling demonstrated significant alterations in both innate and adaptive immune cell populations, including a strong positive correlation between S100A9 expression and Th2 cell abundance. These findings suggest that S100A9 may act as a central regulator linking autophagy deficiency to immune dysregulation in POAG. Its predicted interaction with latanoprost highlights a potential molecular mechanism for pharmacologic modulation of TM homeostasis, supporting the therapeutic value of targeting S100A9-mediated autophagy-immune crosstalk in intraocular pressure control.
[1]Chongqing Med Univ, Affiliated Hosp 1,Ophthalmol Med Ctr, Chongqing Branch,Municipal Div,Natl Clin Res Ctr O, Chongqing Key Lab Prevent & Treatment Major Blindi, Chongqing 400016, Peoples R China.
[2]Wannan Med Coll, Affiliated Hosp 2, Ophthalmol Med Ctr, Wuhu 241000, Anhui, Peoples R China.
[3]Wuhan Univ, Renmin Hosp, Canc Med Ctr, Wuhan 430060, Hubei, Peoples R China.
[4]Wuhan Univ, Renmin Hosp, Ophthalmol Med Ctr, Wuhan 430060, Hubei, Peoples R China.
[5]Wuhan Univ, Affiliated Tongren Hosp, Ophthalmol Med Ctr, Wuhan 430060, Hubei, Peoples R China.
[6]Wannan Med Coll, Sch Clin Med, Wuhu 241002, Anhui, Peoples R China.
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