原发性青光眼病变机制临床实验研究进展

doi:10.3969/j.issn.1673-8640.2019.01.015

摘要/Abstract

摘要：

青光眼是全球首要的不可逆性、致盲性眼病,其发病隐匿,早期症状和体征不典型,容易被忽视,很多患者就诊时已处于疾病中晚期。青光眼主要病理特征为青光眼性视神经损伤。虽然原发性青光眼的病变机制十分复杂,但目前已发现若干与原发性青光眼病变密切相关的重要机制,如机械压迫、血管结构和功能异常、氧化应激、炎症和免疫调节异常。近年来,关键通路和分子相关研究已取得较大进展,临床实验研究也发现了若干与青光眼病变机制相关的、具有潜在临床价值的候选生物学标志物群,希望通过进一步研究使其成为未来临床诊疗的靶点。文章通过回顾原发性青光眼病变机制临床实验研究的进展,以期为临床开展进一步研究提供参考。

关键词: 原发性青光眼, 病变机制, 临床实验研究, 生物学标志物

Abstract:

Glaucoma is a leading cause of irreversible vision loss in the world. Because it may be asymptomatic until the patients are at a relatively late stage and undergo characteristic glaucomatous optic neuropathy,the diagnosis is frequently delayed. Although the pathogenesis of primary glaucoma is complex and diverse,several important pathomechanisms related to primary glaucoma have been discovered,involving mechanical compression,vascular structural and functional damage,oxidative stress,inflammation and immune dysregulation. The research of the key pathways and molecules has made progress. Clinical experimental studies have also identified many candidate biomarker clusters that are potential targets for clinical diagnosis and treatment through further research. This review focuses on the progress of clinical experimental research in the pathogenesis of primary glaucoma to provide a reference for further clinical studies.

Key words: Primary glaucoma, Pathogenesis, Clinical experimental research, Biomarker

中图分类号:

R775.1

马奕综述, 曹文俊, 孙兴怀审校. 原发性青光眼病变机制临床实验研究进展[J]. 检验医学, 2019, 34(1): 71-75.

MA Yi, CAO Wenjun, SUN Xinghuai. Clinical experimental research progress of primary glaucoma pathogenesis[J]. Laboratory Medicine, 2019, 34(1): 71-75.

参考文献 44

[1]	THAM Y C,LI X,WONG T Y,et al.Global prevalence of glaucoma and projections of glaucoma burden through 2040:a systematic review and meta-analysis[J]. Ophthalmology,2014,121(11):2081-2090.
[2]	李若诗,潘英姿. 血管因素与原发性青光眼相关性的研究进展[J]. 中华眼科杂志,2017,53(10):791-796.
[3]	WEINREB R N,AUNG T,MEDEIROS F A.The pathophysiology and treatment of glaucoma:a review[J]. JAMA,2014,311(18):1901-1911.
[4]	CHERECHEANU A P,GARHOFER G,SCHMIDL D,et al.Ocular perfusion pressure and ocular blood flow in glaucoma[J]. Curr Opin Pharmacol,2013,13(1):36-42.
[5]	CHRYSOSTOMOU V,REZANIA F,TROUNCE I A,et al.Oxidative stress and mitochondrial dysfunction in glaucoma[J]. Curr Opin Pharmacol,2013,13(1):12-15.
[6]	RIZZO M I,GRECO A,DE VIRGILIO A,et al.Glaucoma:recent advances in the involvement of autoimmunity[J]. Immunol Res,2017,65(1):207-217.
[7]	JONAS J B,AUNG T,BOURNE R R,et al.Glaucoma[J]. Lancet,2017,390(10108):2183-2193.
[8]	TEZEL G.A proteomics view of the molecular mechanisms and biomarkers of glaucomatous neurodegeneration[J]. Prog Retin Eye Res,2013,35:18-43.
[9]	PASQUALE L R.Vascular and autonomic dysregulation in primary open-angle glaucoma[J]. Curr Opin Ophthalmol,2016,27(2):94-101.
[10]	NIEDZIELSKA E,SMAGA I,GAWLIK M,et al.Oxidative stress in neurodegenerative diseases[J]. Mol Neurobiol,2016,53(6):4094-4125.
[11]	KAMEL K,FARRELL M,O'BRIEN C. Mitochondrial dysfunction in ocular disease:focus on glaucoma[J]. Mitochondrion,2017,35:44-53.
[12]	ASTAFUROV K,ELHAWY E,REN L,et al.Oral microbiome link to neurodegeneration in glaucoma[J]. PLoS One,2014,9(9):e104416.
[13]	TEZEL G.Immune regulation toward immunomodulation for neuroprotection in glaucoma[J]. Curr Opin Pharmacol,2013,13(1):23-31.
[14]	ZABALA L,SALDANHA C,MARTINS E SILVA J,et al. Red blood cell membrane integrity in primary open angle glaucoma:ex vivo and in vitro studies[J]. Eye (Lond),1999,13(Pt 1):101-103.
[15]	MARY A,SERRE I,BRUN J F,et al.Erythrocyte deformability measurements in patients with glaucoma[J]. J Glaucoma,1993,2(3):155-157.
[16]	KILIC-TOPRAK E,TOPRAK I,KILIC-ERKEK O,et al.Increased erythrocyte aggregation in patients with primary open angle glaucoma[J]. Clin Exp Optom,2016,99(6):544-549.
[17]	O'BRIEN C,BUTT Z,LUDLAM C,et al. Activation of the coagulation cascade in untreated primary open-angle glaucoma[J]. Ophthalmology,1997,104(4):725-729.
[18]	LI S,GAO Y,SHAO M,et al.Association between coagulation function and patients with primary angle closure glaucoma:a 5-year retrospective case-control study[J]. BMJ Open,2017,7(11):e016719.
[19]	LI S,CAO W,HAN J,et al.The diagnostic value of white blood cell,neutrophil,neutrophil-to-lymphocyte ratio,and lymphocyte-to-monocyte ratio in patients with primary angle closure glaucoma[J]. Oncotarget,2017,8(40):68984-68995.
[20]	HOYNG P F,DE JONG N,OOSTING H,et al.Platelet aggregation,disc haemorrhage and progressive loss of visual fields in glaucoma. A seven year follow-up study on glaucoma[J]. Int Ophthalmol,1992,16(2):65-73.
[21]	RESCH H,GARHOFER G,FUCHSJÄGER-MAYRL G,et al. Endothelial dysfunction in glaucoma[J]. Acta Ophthalmol,2009,87(1):4-12.
[22]	LI S,ZHANG A,CAO W,et al.Elevated plasma endothelin-1 levels in normal tension glaucoma and primary open-angle glaucoma:a meta-analysis[J]. J Ophthalmol,2016,2016:2678017.
[23]	XU F,ZHAO X,ZENG S M,et al.Homocysteine,B vitamins,methylenetetrahydrofolate reductase gene,and risk of primary open-angle glaucoma:a meta-analysis[J]. Ophthalmology,2012,119(12):2493-2499.
[24]	BURGESS L G,UPPAL K,WALKER D I,et al.Metabolome-wide association study of primary open angle glaucoma[J]. Invest Ophthalmol Vis Sci,2015,56(8):5020-5028.
[25]	RONG S,LI Y,GUAN Y,et al.Long-chain unsaturated fatty acids as possible important metabolites for primary angle-closure glaucoma based on targeted metabolomic analysis[J]. Biomed Chromatogr,2017,31(9):e3963.
[26]	BENOIST D'AZY C,PEREIRA B,CHIAMBARETTA F,et al. Oxidative and anti-oxidative stress markers in chronic glaucoma:a systematic review and meta-analysis[J]. PLoS One,2016,11(12):e0166915.
[27]	GOYAL A,SRIVASTAVA A,SIHOTA R,et al.Evaluation of oxidative stress markers in aqueous humor of primary open angle glaucoma and primary angle closure glaucoma patients[J]. Curr Eye Res,2014,39(8):823-829.
[28]	MAJSTEREK I,MALINOWSKA K,STANCZYK M,et al.Evaluation of oxidative stress markers in pathogenesis of primary open-angle glaucoma[J]. Exp Mol Pathol,2011,90(2):231-237.
[29]	LI S,SHAO M,LI D,et al.Association of serum uric acid levels with primary open-angle glaucoma:a 5-year case-control study[J]. Acta Ophthalmol,2018. [Epub ahead of print]
[30]	LI S,SHAO M,TANG B,et al.The association between serum uric acid and glaucoma severity in primary angle closure glaucoma:a retrospective case-control study[J]. Oncotarget,2017,8(2):2816-2824.
[31]	NUCCI C,DI PIERRO D,VARESI C,et al.Increased malondialdehyde concentration and reduced total antioxidant capacity in aqueous humor and blood samples from patients with glaucoma[J]. Mol Vis,2013,19:1841-1846.
[32]	SORKHABI R,GHORBANIHAGHJO A,JAVADZADEH A,et al.Oxidative DNA damage and total antioxidant status in glaucoma patients[J]. Mol Vis,2011,17:41-46.
[33]	CHUA J,VANIA M,CHEUNG C M,et al.Expression profile of inflammatory cytokines in aqueous from glaucomatous eyes[J]. Mol Vis,2012,18:431-438.
[34]	HUANG P,QI Y,XU Y S,et al.Serum cytokine alteration is associated with optic neuropathy in human primary open angle glaucoma[J]. J Glaucoma,2010,19(5):324-330.
[35]	LI S,CHEN Y,SHAO M,et al.Association of plasma complement C3 levels with primary angle-closure glaucoma in older women[J]. Invest Ophthalmol Vis Sci,2017,58(1):682-689.
[36]	VON THUN UND HOHENSTEIN-BLAUL N,KUNST S,PFEIFFER N,et al. Biomarkers for glaucoma:from the lab to the clinic[J]. Eye (Lond),2017,31(2):225-231.
[37]	TEZEL G,THORNTON I L,TONG M G,et al.Immunoproteomic analysis of potential serum biomarker candidates in human glaucoma[J]. Invest Opthalmol Vis Sci,2012,53(13):8222-8231.
[38]	JANSSEN S F,GORGELS T G,RAMDAS W D,et al.The vast complexity of primary open angle glaucoma:disease genes,risks,molecular mechanisms and pathobiology[J]. Prog Retin Eye Res,2013,37:31-67.
[39]	万雅妮,曹文俊. 原发性闭角型青光眼的分子生物学研究进展[J]. 检验医学,2018,33(4):359-364.
[40]	唐冰花,曹文俊. 原发性开角型青光眼易感基因研究中GWAS的应用[J]. 检验医学,2016,31(4):329-333.
[41]	FINGERT J H,HÉON E,LIEBMANN J M,et al. Analysis of myocilin mutations in 1 703 glaucoma patients from five different populations[J]. Hum Mol Genet,1999,8(5):899-905.
[42]	REZAIE T,CHILD A,HITCHINGS R,et al.Adult-onset primary open-angle glaucoma caused by mutations in optineurin[J]. Science,2002,295(5557):1077-1079.
[43]	MONEMI S,SPAETH G,DASILVA A,et al.Identification of a novel adult-onset primary open-angle glaucoma (POAG) gene on 5q22.1[J]. Hum Mol Genet,2005,14(6):725-733.
[44]	SHIGA Y,AKIYAMA M,NISHIGUCHI K M,et al.Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma[J]. Hum Mol Genet,2018,27(8):1486-1496.