线粒体功能障碍与角膜疾病研究进展
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摘要
角膜是眼光学系统的重要组成部分,角膜疾病则是引起眼部刺激、不适及视力下降的重要原因。越来越多的研究表明,某些角膜疾病与线粒体功能障碍有关。正常角膜自身具有一套氧化与抗氧化应激系统。先天或后天长时间暴露于外界紫外线和高氧环境等原因,角膜内的氧化与抗氧化应激水平失衡,线粒体DNA突变并逐渐积累,最终角膜细胞能量产生障碍引起临床疾病。本文就线粒体功能障碍与某些遗传角膜疾病以及后天性角膜疾病的关系进行总结,旨在阐明氧化应激和粒体功能障碍在角膜疾病中作用,指导相关疾病靶向治疗药物的开发和应用。
Cornea is an important part of the optical system of the eye, and corneal disease is a vital cause of eye irritation, discomfort, and loss of vision. More and more studies have shown that corneal diseases are related to mitochondrial dysfunction. Normally, the cornea itself has a system of oxidative and antioxidant stress. Due to long-time exposure to ultraviolet rays and hyperoxia, the level of oxidative and antioxidative stress in cornea is unbalanced. The mitochondrial DNA(mtDNA) mutated and accumulated gradually, leading to corneal energy dysfunction and related clinical diseases. This review makes a summary on the relationship between mitochondrial dysfunction and inherited and acquired corneal diseases, and we hope to deepen the understanding the role of oxidative stress and mitochondrial dysfunction in corneal diseases and provide guidance for the development and application of targeted drugs for related diseases.
Cornea is an important part of the optical system of the eye, and corneal disease is a vital cause of eye irritation, discomfort, and loss of vision. More and more studies have shown that corneal diseases are related to mitochondrial dysfunction. Normally, the cornea itself has a system of oxidative and antioxidant stress. Due to long-time exposure to ultraviolet rays and hyperoxia, the level of oxidative and antioxidative stress in cornea is unbalanced. The mitochondrial DNA(mtDNA) mutated and accumulated gradually, leading to corneal energy dysfunction and related clinical diseases. This review makes a summary on the relationship between mitochondrial dysfunction and inherited and acquired corneal diseases, and we hope to deepen the understanding the role of oxidative stress and mitochondrial dysfunction in corneal diseases and provide guidance for the development and application of targeted drugs for related diseases.
引文
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[14]DE B P,LABORANTE A,PIZZICOLI C,STALLONE R,LONGOC,MAZZILLI E,et al.Mutational screening of VSX1,SPARC,SOD1,LOX,and TIMP3 in keratoconus[J].Mol Vis,2011,17(268-269):2482-2494.
[15]ABUAMERO K K,AZAD T A,KALANTAN H,SULTAN T,AIMUAMMAR A M.Mitochondrial sequence changes in keratoconus patients[J].Invest Ophthalmol Vis Sci,2014,55(3):1706-1710.
[16]HASBY E A,SAAD H A.Immunohistochemical expression of Fas ligand(Fas L)and neprilysin(Neutral endopeptidase/CD10)in keratoconus[J].Int Ophthalmol,2013,33(2):125-131.
[17]ZHANG L J,XIE L X.Light and transmission electron microscopy study on keratoconus croneas[J].Chin Ophthal Res,2002,20(6):527-529.张立军,谢立信.圆锥角膜的光镜及透射电镜研究[J].眼科研究,2002,20(6):527-529.
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[19]SMITH V A,MATTHEWS F J,MAJID M A,COOK S D.Keratoconus:matrix metalloproteinase-2 activation and TIMP modulation[J].Biochim Biophys Acta,2006,1762(4):431-439.
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[21]WOJCIK K A,KAMINSKA A,BLASIAK J,SCAFLIK J,SZAFLIKJ P.Oxidative stress in the pathogenesis of keratoconus and Fuchs endothelial corneal dystrophy[J].Int J Mol Sci,2013,14(9):19294-19308.
[22]WOJCIK K A,SYNOWIEC E,POLAKOWSKI P,BLASIAK J,SCAFLIK J,SZAFLIK J P.Variation in DNA base excision repair genes in Fuchs endothelial corneal dystrophy[J].Med Sci Monit,2015,21(287):2809-2827.
[23]SANTOS J H,HUNAKOVA L,CHEN Y,BORTNER C,VANHOUTEN B.Cell sorting experiments link persistent mitochondrial DNA damage with loss of mitochondrial membrane potential and apoptotic cell death[J].J Biol Chem,2003,278(3):1728-1734.
[24]WEN Q,FAN Y J.UVB damage and protection effect of ascorbic acid on human corneal endothelial cells in vitro[J].J Shangdong Univ(Nat Sci),2015,50(9):1-6.温茜,樊廷俊.体外培养人角膜内皮细胞的UVB损伤及抗坏血酸的抗氧化保护作用研究[J].山东大学学报(理学版),2015,50(9):1-6.
[25]LIU X F,ZHOU D D,XIE T,MALIK T H,LU C B,LI H J,et al.Nrf2,a potential therapeutic target against oxidative stress in diseases[J].Oxi Med Cell Longev,2017(18):1-9.
[26]ZIAEI A,SCHMEDT T,CHEN Y,JURKUNAS UV.Sulforaphane decreases endothelial cell apoptosis in fuchs endothelial corneal dystrophy:a novel treatment[J].Invest Ophthalmol Vis Sci,2013,54(10):6724-6734.
[2]ZHU R X,ZHANG H.Recent advances in anti-VEGF therapy for corneal neovascularization[J].Rec Adv Ophthalmol,2014,34(7):691-694.朱瑞曦,张红.抗血管内皮生长因子治疗角膜新生血管的研究进展[J].眼科新进展,2014,34(7):691-694.
[3]LASCARATOS G,GARWAY-HEALTH D F,WILLOUGHBY C E,CHAU K Y,SCHAPIRA A H.Mitochondrial dysfunction in glaucoma:Understanding genetic influences[J].Mitochondrion,2012,12(2):202-12.
[4]XUAN M,WANG S,LIU X,HE Y,LI Y,ZHANG Y.Proteins of the corneal stroma:importance in visual function[J].Cell Tissue Res,2016,364(1):9-16.
[5]DIEBOLD L,CHANDEL N S.Mitochondrial ROS regulation of proliferating cells[J].Free Radic Biol Med,2016,100(11):86-93.
[6]CEJKA C,CEJKOVA J.Oxidative stress to the cornea,changes in corneal optical properties,and advances in treatment of corneal oxidative injuries[J].Oxid Med Cell Longev,2015,2015(16):530-591.
[7]PHADKE M,LOKESHWAR M R,BHUTADA S,Tampi C,Saxena R,Kohli S,et al.Retraction note to:kearns sayre syndrome-case report with review of literature[J].Indian J Pediatr,2013,80(11):982.
[8]FINSTERER J,SCORZA F A,SCORZA C A.Broad phenotypic heterogeneity and multisystem involvement in single mt DNA deletionassociated pearson syndrome[J].Med Arch,2018,72(3):234-236.
[9]HO J,PACAUD D,RAKIC M,KHAN.Diabetes in pediatric patients with kearns-sayre syndrome:clinical presentation of 2 cases and a review of pathophysiology[J].Can J Diabetes,2014,38(4):225-228.
[10]KYRIACOU K,KYRIAKIDES T.Mitochondrial encephalomyo-pathies:a review of routine morphological diagnostic methods with emphasis on the role of electron microscopy[J].J Submicrosc Cytol Pathol,2006,38(2-3):201-208.
[11]AI M E,AI H S,NASSER M.Mitochondrial disorders with significant ophthalmic manifestations[J].Middle East Afr J Ophthalmol,2008,15(2):81-86.
[12]KENNEY M C,BROWN D J,RAJERV B.Everett kinsey lecture.The clusive causes of keratoconus:a working hypothesis[J].CLAO J,2000 26(1):10-13.
[13]PATHAK D,NAYAK B,SINGH M,Sharma N,Tandon R,Sinha R,et al.Mitochondrial complex 1 gene analysis in keratoconus[J].Mol Vis,2011,17(1):1514-1525.
[14]DE B P,LABORANTE A,PIZZICOLI C,STALLONE R,LONGOC,MAZZILLI E,et al.Mutational screening of VSX1,SPARC,SOD1,LOX,and TIMP3 in keratoconus[J].Mol Vis,2011,17(268-269):2482-2494.
[15]ABUAMERO K K,AZAD T A,KALANTAN H,SULTAN T,AIMUAMMAR A M.Mitochondrial sequence changes in keratoconus patients[J].Invest Ophthalmol Vis Sci,2014,55(3):1706-1710.
[16]HASBY E A,SAAD H A.Immunohistochemical expression of Fas ligand(Fas L)and neprilysin(Neutral endopeptidase/CD10)in keratoconus[J].Int Ophthalmol,2013,33(2):125-131.
[17]ZHANG L J,XIE L X.Light and transmission electron microscopy study on keratoconus croneas[J].Chin Ophthal Res,2002,20(6):527-529.张立军,谢立信.圆锥角膜的光镜及透射电镜研究[J].眼科研究,2002,20(6):527-529.
[18]GALVIS V,SHERWIN T,TELLO A,MERAYO J,BARRERA R,ACERA A,et al.Keratoconus:an inflammatory disorder[J]?Eye,2015,29(7):843-859.
[19]SMITH V A,MATTHEWS F J,MAJID M A,COOK S D.Keratoconus:matrix metalloproteinase-2 activation and TIMP modulation[J].Biochim Biophys Acta,2006,1762(4):431-439.
[20]ARNAL E,PERIS-MARTINEZ C,MENEZO J L,JOHNSEN-SOR-IANO S,ROMERO F J.Oxidative stress in keratoconus[J]?Invest Ophthalmol Vis Sci,2011(52):8592-8597.
[21]WOJCIK K A,KAMINSKA A,BLASIAK J,SCAFLIK J,SZAFLIKJ P.Oxidative stress in the pathogenesis of keratoconus and Fuchs endothelial corneal dystrophy[J].Int J Mol Sci,2013,14(9):19294-19308.
[22]WOJCIK K A,SYNOWIEC E,POLAKOWSKI P,BLASIAK J,SCAFLIK J,SZAFLIK J P.Variation in DNA base excision repair genes in Fuchs endothelial corneal dystrophy[J].Med Sci Monit,2015,21(287):2809-2827.
[23]SANTOS J H,HUNAKOVA L,CHEN Y,BORTNER C,VANHOUTEN B.Cell sorting experiments link persistent mitochondrial DNA damage with loss of mitochondrial membrane potential and apoptotic cell death[J].J Biol Chem,2003,278(3):1728-1734.
[24]WEN Q,FAN Y J.UVB damage and protection effect of ascorbic acid on human corneal endothelial cells in vitro[J].J Shangdong Univ(Nat Sci),2015,50(9):1-6.温茜,樊廷俊.体外培养人角膜内皮细胞的UVB损伤及抗坏血酸的抗氧化保护作用研究[J].山东大学学报(理学版),2015,50(9):1-6.
[25]LIU X F,ZHOU D D,XIE T,MALIK T H,LU C B,LI H J,et al.Nrf2,a potential therapeutic target against oxidative stress in diseases[J].Oxi Med Cell Longev,2017(18):1-9.
[26]ZIAEI A,SCHMEDT T,CHEN Y,JURKUNAS UV.Sulforaphane decreases endothelial cell apoptosis in fuchs endothelial corneal dystrophy:a novel treatment[J].Invest Ophthalmol Vis Sci,2013,54(10):6724-6734.