A highly sensitive fluorescent probe RN-NA reveals peroxynitrite as a novel biomarker for primary open angle glaucoma  

作　　者：Bo Qin Yuan Lei Luo Bao You-Jia Zhang Ke-Yin Liu Yu-Hong Chen 

机构地区：[1]Department of Ophthalmology&Visual Science,Eye&ENT Hospital,Shanghai Medical College,Fudan University,Shanghai 200031,China [2]Key Laboratory of Myopia,NHFPC(Fudan University),Shanghai Key Laboratory of Visual Impairment and Restoration(Fudan University),Shanghai 200031,China [3]State Key Laboratory of Biobased Material and Green Papermaking,Key Laboratory of Pulp&Paper Science and Technology of Shandong Province/Ministry of Education,Qilu University of Technology,Shandong Academy of Sciences,Jinan 250353,Shandong Province,China

出　　处：《International Journal of Ophthalmology(English edition)》2024年第2期219-227,共9页国际眼科杂志（英文版）

基　　金：Supported by the National Natural Science Foundation of China(No.81870692,No.82070959,No.82271082);the Shanghai Committee of Science and Technology,China(No.20S31905800);Clinical Research Plan of SHDC(No.SHDC2020CR6029).

摘　　要：AIM:To directly quantify peroxynitrite(ONOO-)using a highly sensitive fluorescence resonance energy transfer probe RN-NA,investigate the association between ONOOand primary open angle glaucoma(POAG),and clarify whether RN-NA could be used as a potential tool for POAG diagnosis.METHODS:Plasma and aqueous humor(AH)samples were collected from POAG patients(n=100,age:59.70±6.87y)and age-related cataract(ARC)patients(n=100,age:61.15±4.60y)admitted to our hospital.Next,RN-NA was used to detect ONOO-in plasma and AH samples,and the relationship between ONOO-level and POAG was analyzed using binary logistic regression.Besides,Pearson correlation analysis was applied to characterize the correlation of the levels of ONOO-with the patients’age,intraocular pressure(IOP),and mean deviation of visual field testing.The ONOO-scavenger MnTMPyP was employed to treat the 3-morpholinosyndnomine(SIN-1)-induced ocular hypertension in mice(n=7,6-8wk).Finally,the IOP and ONOO-in both eyes were measured 30min after the last drug treatment.RESULTS:ONOO-levels of AH and plasma were significantly higher in the POAG group than in the ARC group(P<0.01).Additionally,ONOO-levels were closely correlated with POAG in a binary logistic regression analysis[odds ratio(OR)=1.008,95%confidence interval(CI):1.002-1.013,P<0.01 for AH;OR=1.004,95%CI:1.002-1.006,P<0.001 for plasma].Pearson correlation analysis showed that ONOO-levels in AH or plasma were positively associated with visual field defects(R=0.51,P<0.01 for AH;R=0.45,P<0.001 for plasma),and ONOO-levels in plasma and AH were correlated in the POAG group(R=0.69,P<0.001).However,administering MnTMPyP to mouse eyes reversed the elevated IOP caused by SIN-1(P<0.05).CONCLUSION:ONOO-levels in AH and plasma,detected by RN-NA,are significantly related to POAG and positively correlated with visual field defects in POAG patients.Hence,ONOO-is a potential biomarker of POAG,especially advanced POAG.Besides,anti-nitration compounds may be novel ocular hypotensive agents based on the animal study.

关 键 词：PEROXYNITRITE fluorescent probe RN-NA primary open angle glaucoma 3-morpholinosyndnomine 

分 类 号：R775[医药卫生—眼科]