To investigate the association between systemic nitrotyrosine (NT) levels and primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) and the mechanism involved. A case control study was conducted in the Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Fudan University from April 2017 to December 2017. A total of 400 participants were consecutively recruited into this study (100 PACG, 100 POAG and 200 controls). Multivariable logistic regression analysis was performed to identify the association between serum NT level and PACG or POAG. Clinical results were validated in cell and animal models. Among 200 glaucoma patients, 101 (50.5%) were women; the age was 57.07 ± 14.51 years. 106 (53%) control participants were women and age was 58.34 ± 14.04 years. Serum levels of NT in PACG and POAG patients are significantly higher than controls (1808.53 ± 417.76 nmol/L vs. 1270.62 ± 454.60 nmol/L, p < 0.001; 1718.63 ± 437.29 nmol/L vs. 1258.38 ± 460.72 nmol/L, p < 0.001). Further, elevated serum NT level increases the risk of developing PACG (OR = 1.003, 95% CI: 1.002 to 1.004, p < 0.001) and POAG (OR = 1.002, 95% CI: 1.002 to 1.003, p < 0.001). Consistent with the clinical data, serum and aqueous humour NT levels are significantly higher in caveolin 1 knockout (Cav1 KO) mice, an animal model of glaucoma. More importantly, peroxynitrite (PN) scavenger MnTMPyP and its transduction molecule PARP inhibitor significantly reduce intraocular pressure in Cav1 KO mice. Our data show for the first time that NT is a systemic risk factor and local treatment target of glaucoma.

中文翻译：

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过氧亚硝酸盐是青光眼的一种新型危险因素和治疗靶标。

目的探讨全身性硝基酪氨酸（NT）水平与原发性闭角型青光眼（PACG）和原发性开角型青光眼（POAG）之间的相关性及其机制。病例对照研究于2017年4月至2017年12月在复旦大学附属眼与耳鼻喉科医院眼科和视觉科学系进行。总共招募了400名参与者（100名PACG，100名POAG和200名对照） 。进行多变量logistic回归分析以鉴定血清NT水平与PACG或POAG之间的关联。临床结果在细胞和动物模型中得到验证。在200例青光眼患者中，有101例（50.5％）是女性；年龄为57.07±14.51岁。106名（53％）对照参与者为女性，年龄为58.34±14.04岁。PACG和POAG患者的血清NT水平显着高于对照组（1808.53±417.76 nmol / L与1270.62±454.60 nmol / L，p <0.001; 1718.63±437.29 nmol / L与1258.38±460.72 nmol / L，p <0.001）。此外，升高的血清NT水平增加了发生PACG（OR ＝ 1.003，95％CI：1.002至1.004，p ＜0.001）和POAG（OR ＝ 1.002，95％CI：1.002至1.003，p ＜0.001）的风险。与临床数据一致，青光眼动物模型小窝蛋白1基因敲除（Cav1 KO）小鼠的血清和房水NT水平显着升高。更重要的是，过氧亚硝酸盐（PN）清除剂MnTMPyP及其转导分子PARP抑制剂可显着降低Cav1 KO小鼠的眼压。我们的数据首次显示NT是青光眼的系统性危险因素和局部治疗目标。