Peroxynitrite is a novel risk factor and treatment target of glaucoma.
Nitric Oxide
; 99: 17-24, 2020 06 01.
Article
in En
| MEDLINE
| ID: mdl-32222418
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tyrosine
/
Glaucoma, Angle-Closure
/
Glaucoma, Open-Angle
/
Peroxynitrous Acid
/
Metalloporphyrins
Type of study:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Nitric Oxide
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2020
Document type:
Article