Aqueous humor lipidomic profile in primary open angle glaucoma patients

Abstract

Purpose : To identify the aqueous humor (AH) profile of lipid mediators in primary open angle glaucoma (POAG) eyes compared to those without glaucoma

Methods : AH samples from eyes with and without glaucoma underwent lipidomic analyses using liquid chromatography-mass spectrometry (LC-MS). Glaucoma samples were obtained from 60-80-year-old POAG patients undergoing a glaucoma surgery with or without cataract surgery. Matched control samples were obtained from patients undergoing routine cataract surgery. Patients with diabetes mellitus, systemic inflammatory disease, uveitis, retinopathy and age-related macular degeneration and those on Aspirin were excluded. From each eye, 100 mL of AH was collected using a 30 Gauge needle mounted on a 1-mL syringe, introduced into the anterior chamber anterior to the limbus, prior to any surgical intraocular entry. The samples were immediately snap frozen on dry ice and stored at -80C until assessment by lipidomic analyses of a panel of 40 polyunsaturated fatty acids (PUFA), metabolites and lipid mediators. All participants signed an informed consent. This study was approved by the University Health Network and Kensington Eye Institute Research and Ethics Boards.

Results : AH was collected from 16 and 18 eyes with and without glaucoma, respectively. The mean age was 68.7±6.4 years for the glaucoma group and 71.0±4.7 years for the control group (p=0.25). The mean preoperative intraocular pressure 14.1±3.1 and 15.2±1.6 mmHg for the glaucoma and control groups, respectively (p=0.24). The cup-to-disc ratios were 0.9±0.1 and 0.3±0.1 for the glaucoma and control groups, respectively (p<0.001). All 16 glaucoma eyes received prostaglandin analogue eye drops prior to surgery; 15 were on beta-blocker eye drops. There were statistically significant differences between glaucomatous and control eyes for arachidonic acid (1328.0±322.0 vs 643.1±130.6, p=0.001), lipoxin A₄ (0.79±0.14 vs 0.32±0.10, p=0.01) and 12-hydoxyeicosapentanoic acid (0.35±0.17 vs undetected, p=0.04). Substantial levels, but no significant differences, were identified for docosahexanoic acid (212.0±46.33 vs 131.1±22.36, p=0.11), eicosapentanoic acid (6.21±1.40 vs 3.76±0.32, p=0.08), prostaglandin E₂ (2.83±1.92 vs undetected, p=0.13) and prostaglandin D₂ (2.43±1.49 vs 0, p=0.09).

Conclusions : Increased levels of lipid mediators are present in glaucomatous eyes. Arachidonic acid metabolites may play a role in glaucoma pathogenesis.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.