Inducible and Endothelial Nitric Synthetase Expression and Nitrotyrosine Accumulation in Iris Vasculature of Patients with Primary Open-Angle Glaucoma: A Pilot Study

BACKGROUND: The “double-faced” effect of nitric oxide (NO) is thought to play an important role in triggering and progression of glaucoma. MATERIAL/METHODS: Iris samples were obtained during iridectomy in 35 patients (mean age of 65.4±5.3 years) with diagnosed primary open-angle glaucoma (POAG). The controls were collected postmortem from 10 donors with a mean age of 62.2±1.9 years. Visual field defects were evaluated by perimetry. The Hodapp-Parrish-Anderson classification was used to divide patients into 3 visual field defect groups. The intraocular pressure was measured 3 times before surgery using applanation tonometry. The phenotype activity of nitric oxide synthase (NOS) isoenzymes (endothelial – eNOS and inducible – iNOS) and expression of nitrotyrosine in iris vasculature was assessed. RESULTS: Significant differences were found between glaucoma patients and the controls in eNOS and iNOS activity (Mann-Whitney test, U=35.5, Z=−2.037, p=0.04 and U=21, Z=2.69, p=0.007, respectively). In addition, the results showed an upregulation of nitrotyrosine in the capillary endothelial cells in the study group, which was associated with the duration of diagnosed glaucoma (R-Spearman of 0.33, p=0.0047) and visual field mean defect MD (R-Spearman of 0.29, p=0.019). Moreover, the activity of nitrotyrosine was significantly correlated with iNOS immunoreactivity (R-Spearman of 0.5, p=0.0001). However, the iNOS activity significantly varied among Hodapp-Parrish-Anderson groups (p=0.03). CONCLUSIONS: Our observations confirmed the association between glaucomatous disturbances and upregulation of iNOS, together with increased nitrotyrosine storage.