Elevated histamine levels in aqueous humor of patients with glaucoma

PURPOSE: Neurotransmitters (NTs) are the key mediators of essential ocular functions, such as processing the visual functions of the retina, maintaining homeostasis of aqueous humor, and regulating ocular blood flow. This study aims to determine variations in the levels of L-glutamate and γ-aminobutyric acid (GABA), histaminergic, adrenergic, cholinergic, and serotonergic NTs in patients with primary glaucoma versus patients with cataract. METHODS: This case–control study involved three age-matched groups of patients with primary open angle glaucoma (POAG, n = 14), primary angle closure glaucoma (PACG, n = 21), and cataract (control, n = 19). Patients’ aqueous humor and plasma were collected, snap frozen at −80 °C, and subjected to ultrasensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis for quantification of NTs. RESULTS: Baseline intraocular pressure and the cup-to-disc ratio were found to be statistically significantly elevated in the POAG and PACG groups compared to the cataract control group. In aqueous humor, histamine was found to be statistically significantly elevated (5-fold, p<0.0001), whereas 1-methyl histamine was statistically significantly decreased (p<0.05) in POAG compared to the control group. A statistically significant increase in L-glutamate and GABA was observed among both patient groups with glaucoma compared to the cataract control group. Adrenaline was found to be elevated only in the PACG group (2.7-fold, p<0.05). No statistically significant difference was observed among the plasma NT levels between the groups. CONCLUSIONS: This study demonstrated the prominent role of the histaminergic system apart from autonomic mechanisms in the progression of glaucoma. Elevated L-glutamate and GABA could be due to retinal ganglionic cell death. Further studies are required to evaluate the effects of histamine on Müller cell dysfunction.