Profiling lipidomic variations in primary open-angle and angle-closure glaucoma patients

Retinal ganglion cell death in glaucoma leads to progressive and irreversible vision loss. Investigating lipidomic profiles of aqueous humor and plasma from primary glaucoma patients may reveal novel lipid signaling pathways and biomarkers. Plasma lipidomics was included to assess systemic alterations, enabling comparison with ocular changes and explore accessible, minimally invasive biomarker sources. This study included patients with primary open-angle glaucoma (POAG), angle-closure glaucoma (PACG), and cataract controls (n = 20 in each group). Serum lipid screening was conducted via biochemical analyzer. Aqueous humor and plasma samples were collected, and lipids were extracted and analyzed using high-resolution mass spectrometry (HRMS). Spectral identification and relative quantification of lipid species were performed with LipidSearch™ver_4.1. The percentage of altered species within each lipid class was analyzed with a log₂fold change (FC) threshold ≥1/≤-1. Data normalization and multivariate statistical analyses were conducted using MetaboAnalyst 5.0 with significance criteria (log₂ FC ≥ 1/≤-1, p < 0.05 and variable importance in projection (VIP) > 1). No significant changes were observed in routine serum lipid profiles of glaucoma patients versus controls. In aqueous humor, phosphatidylcholines and lysophosphatidylcholines (>50 %) were elevated in aqueous humor of both glaucoma groups, while sphingomyelins (>85 %) and ceramides (18.75 %) were specifically elevated in PACG. Of 301 lipid species identified in aqueous humor, 51 met significance (POAG: 24, PACG: 27). In plasma, diglycerides (>20 %), triglycerides and cholesterol esters (>10 %, log₂FC ≤ -1) were declined in both glaucoma groups than controls. Of 1762 plasma lipids identified, 100 met significance (POAG: 47, PACG: 53). Sphingomyelin and ceramide alterations in PACG aqueous humor suggested disrupted mechanosignaling mechanisms. Altered phosphatidylcholines, lysophosphatidylcholines and glycerides linked with retinal-degeneration and apoptosis in both glaucomatous conditions.