Elevated Histamine Levels in the Aqueous Humor of the Patients with Primary Open Angle Glaucoma

Abstract

Purpose : To determine variations in the levels of both excitatory (L-glutamate) & inhibitory (GABA) neurotransmitters (NTs), Histaminergic NTs (histamine and 1-methyl histamine), Adrenergic (noradrenaline, adrenaline, DOPA & dopamine), Cholinergic (acetylcholine) and Serotonergic (serotonin and N-acetyl serotonin) NTs in primary glaucomatous versus cataract patients.

Methods : This preliminary case-control study involved the three age-matched groups of patients with primary open angle glaucoma (POAG, n=14), primary angle closure glaucoma (PACG, n=21) and cataract patients (control, n=19). Patient’s aqueous humor (70 to 100 μL) was collected by paracentesis during the trabeculectomy and cataract surgery and the plasma (2 ml) of the same patients was collected one hour before the surgery, stored at -80 degree. Aqueous humor and plasma were subjected for ultrasensitive LC-MS/MS analysis for the quantification of neurotransmitters.

Results : Baseline intraocular pressure and cup-to-disc ratio was found significantly elevated in both the glaucomatous groups as compared to the control group. In aqueous humor, histamine was found to be significantly elevated (5-fold, p<0.0001) whereas 1-methyl histamine was significantly decreased (p<0.05) in POAG as compared to the control. Significant increase in L-glutamate and GABA has been observed among both the glaucomatous patient groups as compared to the cataract control. Adrenaline was found to be elevated only in the PACG group (2.7-fold, p<0.05). Significant difference was observed among the compared plasma NT levels between the groups.

Conclusions : This study demonstrated the prominent role of histaminergic system apart from autonomic mechanisms in the progression of glaucoma. Elevated L-glutamate and GABA showed their release could be the result of the retinal ganglionic cell death. Further studies are required to evaluate the effects of histamine on Müller cell dysfunction.

This is a 2021 ARVO Annual Meeting abstract.