山东大学耳鼻喉眼学报 ›› 2021, Vol. 35 ›› Issue (5): 125-131.doi: 10.6040/j.issn.1673-3770.0.2020.449

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感染性角膜炎的模型制备

闫语1,2,曾澳1,2，何宇茜1   

  1. 1.吉林大学第二医院 眼科中心, 吉林 长春 130041;
    2.吉林大学白求恩医学部, 吉林 长春 130021
  • 发布日期:2021-09-29
  • 通讯作者: 何宇茜. E-mall:heyuxihot@163.com
  • 基金资助:
    吉林省科技厅国际科技合作项目(20200801016GH);吉林省医疗卫生人才专项项目(2019SCZT052,2019SCZT057);吉林大学优秀青年教师培养计划(419080500586,419080520252);吉林省科技厅自然科学基金(20180101146JC);吉林省财政厅青年人才培养项目(3D5197389429);吉林省中医药科技资助项目(2019134);BMP4抑制角膜新生血管的机制研究(3R2196623429);专业学位研究生课程案例库(419100200379);吉林省科技厅国际科技合作项目(20180414063GH);吉林省教育厅科学技术研究项目(JJKH20201103KJ);吉林大学基本科研业务费项目(45119031C004);吉林省卫生专项项目(2020SCZT089)

Model preparation of infectious keratitis

YAN Yu1,2, ZENG Ao1,2,HE Yuxi1   

  1. 1. Department of Ophthalmology, the Second Hospital of Jilin University, Changchun 130041, Jilin, China;
    2. Norman Bethune Health Science Center of Jilin University, Changchun 130021, Jilin, China
  • Published:2021-09-29

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摘要： 感染性角膜炎是一种由致病微生物侵袭角膜组织引起的炎症,是世界性的常见致盲眼病,主要致病的病原体有细菌、真菌、病毒和棘阿米巴。其中,细菌感染是感染性角膜炎的主要原因,但近年来真菌性角膜炎有逐年增多趋势。目前的有效治疗手段主要是根据致病微生物不同,以局部使用或结膜下注射抗细菌和真菌制剂及全身运用抗病毒药物为主。综述从菌液制备、操作方法到评分检测方法系统地阐述了由细菌、真菌、病毒和棘阿米巴引起的角膜炎的模型制备。就如何制备出具有针对性的动物模型进行探讨,为评价及发掘治疗感染性角膜炎的治疗效果和不良反应提供依据。

关键词: 感染性角膜炎, 动物模型, 真菌性角膜炎, 细菌性角膜炎

Abstract: Infectious keratitis is an inflammation caused by the invasion of pathogenic microorganisms on corneal tissue. It is a common cause of blindness in the world. The main pathogenic microorganisms are bacteria, fungi, viruses, and Acanthamoeba. Bacteria is the main cause of infectious keratitis, but fungal keratitis has been increasing year by year in recent years. At present, the effective treatment is local use or subconjunctival injection of anti-bacterial and fungal agents, and systemic use of antiviral drugs, based on the different pathogenic microorganisms. We systematically describe models preparation of infectious keratitis caused by bacteria, fungi, viruses, and Acanthamoeba, including the preparation of the bacterial solution, operation methods and scoring detection methods. This paper elaborates how to prepare a targeted animal model to provide theoretical basis for evaluating and exploring the treatment effect and adverse reactions of infectious keratitis.

Key words: Infectious keratitis, Animal model, Fungal keratitis, Bacterial keratitis

中图分类号: 

  • R772.21
[1] 郝文培, 翟华蕾, 孙晓彤, 等. 角膜再移植原因与植片失活的危险因素分析[J]. 山东大学耳鼻喉眼学报, 2020, 34(3):134-140. doi:10.6040/j.issn.1673-3770.0.2019.605. HAO Wenpei, ZHAI Hualei, SUN Xiaotong, et al. Etiology of repeat keratoplasty and risk factors for failure of corneal grafts[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2020, 34(3):134-140. doi:10.6040/j.issn.1673-3770.0.2019.605.
[2] Manikandan P, Abdel-Hadi A, Randhir Babu Singh Y, et al. Fungal keratitis: epidemiology, rapid detection, and antifungal susceptibilities of Fusarium and Aspergillus isolates from cornealscrapings[J]. Biomed Res Int, 2019, 2019:6395840. doi:10.1155/2019/6395840.
[3] Mahmoudi S, Masoomi A, Ahmadikia K, et al. Fungal keratitis: an overview of clinical and laboratory aspects[J]. Mycoses, 2018, 61(12):916-930. doi:10.1111/myc.12822.
[4] Azher TN, Yin XT, Stuart PM. Understanding the role of chemokines and cytokines in experimental models of Herpes simplex keratitis[J]. J Immunol Res, 2017, 2017:1-5. doi:10.1155/2017/7261980.
[5] Como CN, Bubak AN, Blackmon AM, et al. Varicella zoster virus induces differential cell-type specific responses in human corneal epithelial cells and keratocytes[J]. Invest Ophthalmol Vis Sci, 2019, 60(2):704-711. doi:10.1167/iovs.18-25801.
[6] Pinna A, Porcu T, Boscia F, et al. Free-living amoebae keratitis[J]. Cornea, 2017, 36(7):785-790. doi:10.1097/ICO.0000000000001226.
[7] Lorenzo-Morales J, Khan NA, Walochnik J. An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment[J]. Parasite, 2015, 22:10. doi:10.1051/parasite/2015010.
[8] Tolba ME, Huseein EA, Farrag HM, et al. Allovahlkampfia spelaea causing keratitis in humans[J]. PLoS Negl Trop Dis, 2016, 10(7):e0004841. doi:10.1371/journal.pntd.0004841.
[9] Nunes TE, Brazil NT, Fuentefria AM, et al. Acanthamoeba and Fusarium interactions: a possible problem in keratitis[J]. Acta Trop, 2016, 157:102-107. doi:10.1016/j.actatropica.2016.02.001.
[10] Saraswathi P, Beuerman RW. Corneal biofilms: from planktonic to microcolony formation in an experimental keratitis infection with Pseudomonas aeruginosa[J]. Ocul Surf, 2015, 13(4):331-345.doi:10.1016/j.jtos.2015.07.001.
[11] Metruccio MME, Wan SJ, Horneman H, et al. A novel murine model for contact lens wear reveals clandestine IL-1R dependent corneal parainflammation and susceptibility to microbial keratitis upon inoculation with Pseudomonas aeruginosa[J]. Ocul Surf, 2019, 17(1):119-133. doi:10.1016/j.jtos.2018.11.006.
[12] Alarcon I, Tam C, Mun JJ, et al. Factors impacting corneal epithelial barrier function against Pseudomonas aeruginosa traversal[J]. Invest Ophthalmol Vis Sci, 2011, 52(3):1368-1377. doi:10.1167/iovs.10-6125.
[13] Sun Y, Hise AG, Kalsow CM, et al. Staphylococcus aureus-induced corneal inflammation is dependent on Toll-like receptor 2 and myeloid differentiation factor 88[J]. Infect Immun, 2006, 74(9):5325-5332. doi:10.1128/IAI.00645-06.
[14] Tang AH, Caballero AR, Marquart ME, et al. Mechanism of Pseudomonas aeruginosa small protease(PASP), a corneal virulence factor[J]. Invest Ophthalmol Vis Sci, 2018, 59(15):5993-6002. doi:10.1167/iovs.18-25834.
[15] Zhu H, Kochevar IE, Behlau I, et al. Antimicrobial blue light therapy for infectious keratitis: ex vivo and in vivo studies[J]. Invest Ophthalmol Vis Sci, 2017, 58(1):586-593. doi:10.1167/iovs.16-20272.
[16] Barequet IS, Bourla Ni, Pessach YN, et al. Staphylolysin is an effective therapeutic agent for Staphylococcus aureus experimental keratitis[J]. Graefes Arch Clin Exp Ophthalmol, 2012, 250(2):223-229. doi: 10.1007/s00417-011-1822-6.
[17] Bischoff G, Kuhn D. Contact lens complications: Diagnosis and treatment[J]. Ophthalmologe, 2018, 115(12):1087-1102. doi: 10.1007/s00347-018-0812-z.
[18] Metruccio MME, Wan SJ, Horneman H, et al. A novel murine model for contact lens wear reveals clandestine IL-1R dependent corneal parainflammation and susceptibility to microbial keratitis upon inoculation with Pseudomonas aeruginosa[J]. Ocul Surf, 2019, 17(1):119-133. doi:10.1016/j.jtos.2018.11.006.
[19] Wei C, Zhu MF, Petroll WM, et al. Pseudomonas aeruginosa infectious keratitis in a high oxygen transmissible rigid contact lens rabbit model[J]. Invest Ophthalmol Vis Sci, 2014, 55(9):5890. doi:10.1167/iovs.14-14235.
[20] Chucair-Elliott AJ, Gurung HR, Carr MM, et al. Colony stimulating factor-1 receptor expressing cells infiltrating the cornea control corneal nerve degeneration in response to HSV-1 infection[J]. Invest Ophthalmol Vis Sci, 2017, 58(11):4670-4682. doi:10.1167/iovs.17-22159.
[21] Chucair-Elliott AJ, Zheng M, Carr DJJ. Degeneration and regeneration of corneal nerves in response to HSV-1 infection[J]. Investig Ophthalmol Vis Sci, 2015, 56(2):1097-1107. doi:10.1167/iovs.14-15596.
[22] Tsatsos M, MacGregor C, Athanasiadis I, et al. Herpes simplex virus keratitis: an update of the pathogenesis and current treatment with oral and topical antiviral agents[J]. Clin Exp Ophthalmol, 2016, 44(9):824-837. doi:10.1111/ceo.12785.
[23] Chucair-Elliott AJ, Carr MM, Carr DJJ. Long-term consequences of topical dexamethasone treatment during acute corneal HSV-1 infection on the immune system[J]. J Leukoc Biol, 2017, 101(5):1253-1261. doi:10.1189/jlb.4a1116-459r.
[24] Watson ZL, Washington SD, Phelan DM, et al. In vivo knockdown of the Herpes simplex virus 1 latency-associated transcript reduces reactivation from latency[J]. J Virol, 2018, 92(16):e00812-e00818. doi:10.1128/JVI.00812-18.
[25] Varanasi SK, Jaggi U, Hay N, et al. Hexokinase II may be dispensable for CD4 T cell responses against a virus infection[J]. PLoS One, 2018, 13(1):e0191533. doi:10.1371/journal.pone.0191533.
[26] Varanasi SK, Reddy PBJ, Bhela S, et al. Azacytidine treatment inhibits the progression of Herpes stromal keratitis by enhancing regulatory T cell function[J]. J Virol, 2017, 91(7):e02367-e02316. doi:10.1128/JVI.02367-16.
[27] 赵壮红. 单纯疱疹病毒性角膜炎小鼠模型的建立与鉴定[D]. 昆明: 昆明医科大学, 2019.
[28] 姜玉珍, 曾明范, 王兵, 等. 改良深板层角膜移植术治疗大鼠严重基质坏死型单纯疱疹病毒性角膜基质炎的临床效果[J]. 中华医院感染学杂志, 2020, 30(13):2027-2032. doi:10.11816/cn.ni.2020-191504. JIANGYuzhen, ZENG Mingfan, WANG Bing, et al. Clinical effect of modified deep lamellar keratoplasty on treatment of rats with severe stromal necrosis Herpes simplex keratitis[J]. Chin J Nosocomiology, 2020, 30(13):2027-2032. doi:10.11816/cn.ni.2020-191504.
[29] 周洪伟. P物质在小鼠单纯疱疹病毒性角膜炎复发中的作用研究[D]. 武汉: 武汉大学, 2016. ZHOU Hongwei. Experimental study on substance P inhibiting Herpes simplex keratitis recurrence in mouse[D]. Wuhan: Wuhan University, 2016.
[30] Riccio RE, Park SJ, Longnecker R, et al. Characterization of sex differences in ocular herpes simplex virus 1 infection and herpes stromal keratitis pathogenesis of wild-type and herpesvirus entry mediator knockout mice[J]. mSphere, 2019, 4(3): e00322-19. doi:10.1128/mSphere.00322-19(2019).
[31] Dridi S, Richerioux N, Gonzalez Suarez CE, et al. A mutation in the UL24 gene abolishes expression of the newly identified UL24.5 protein of Herpes simplex virus 1 and leads to an increase inpathogenicity in mice[J]. J Virol, 2018, 92(20):e00671-e00618. doi:10.1128/JVI.00671-18.
[32] Davido DJ, Tu EM, Wang H, et al. Attenuated Herpes simplex virus 1(HSV-1)expressing a mutant form of ICP6 stimulates a strong immune response that protects mice against HSV-1-inducedcorneal disease[J]. J Virol, 2018, 92(17):92:e01036-18. doi:10.1128/jvi.01036-18.
[33] Neelam S, Niederkorn JY. Pathobiology and immunobiology of keratitis: insights from animal models[J]. Yale J Biol Med, 2017, 90(2):261-268.
[34] Alizadeh H, Neelam S, Niederkorn JY. Effect of immunization with the mannose-induced acanthamoeba protein and acanthamoeba plasminogen activator in mitigating acanthamoeba keratitis[J]. Invest Ophthalmol Vis Sci, 2007, 48(12):5597. doi:10.1167/iovs.07-0407.
[35] Alizadeh H, Neelam S, Hurt M, et al. Role of contact lens wear, bacterial flora, and mannose-induced pathogenic protease in the pathogenesis of amoebic keratitis[J]. Infect Immun, 2005, 73(2):1061-1068. doi:10.1128/IAI.73.2.1061-1068.2005.
[36] Nakagawa H, Hattori T, Koike N, et al. Investigation of the role of bacteria in the development of Acanthamoeba keratitis[J]. Cornea, 2015, 34(10):1308-1315.doi:10.1097/ICO.0000000000000541.
[37] He YG, McCulley JP, Alizadeh H, et al. A pig model of Acanthamoeba keratitis: transmission via contaminated contact lenses[J]. Invest Ophthalmol Vis Sci, 1992, 33(1):126-133.
[38] Ren MY, Wu XY. Evaluation of three different methods to establish animal models of Acanthamoeba keratitis[J]. Yonsei Med J, 2010, 51(1):121-127. doi:10.3349/ymj.2010.51.1.121.
[39] Ge Z, Qing Y, Zicheng S, et al. Rapid and sensitive diagnosis of Acanthamoeba keratitis by loop-mediated isothermal amplification[J]. Clin Microbiol Infect, 2013, 19(11):1042-1048. doi:10.1111/1469-0691.12149.
[40] Alizadeh H, Tripathi T, Abdi M, et al. Pathogenic strains of Acanthamoeba are recognized by TLR4 and initiated inflammatory responses in the cornea[J]. PLoS One, 2014, 9(3):e92375.doi:10.1371/journal.pone.0092375.
[41] Polat ZA, Obwaller A, Vural A, et al. Efficacy of miltefosine for topical treatment of Acanthamoeba keratitis in Syrian hamsters[J]. Parasitol Res, 2012, 110(2):515-520. doi:10.1007/s00436-011-2515-0.
[42] Alekseev O, Tran AH, Azizkhan-Clifford J. Ex vivo organotypic corneal model of acute epithelial Herpes simplex virus type I infection[J]. J Vis Exp, 2012(69):e3631. doi:10.3791/3631.
[43] Yadavalli T, Agelidis A, Jaishankar D, et al. Targeting Herpes simplex virus-1 gD by a DNA aptamer can be an effective new strategy to curb viral infection[J]. Mol Ther Nucleic Acids, 2017, 9:365-378. doi:10.1016/j.omtn.2017.10.009.
[44] Agelidis AM, Hadigal SR, Jaishankar D, et al. Viral activation of heparanase drives pathogenesis of Herpes simplex virus-1[J]. Cell Rep, 2017, 20(2):439-450. doi:10.1016/j.celrep.2017.06.041.
[45] Richard NR, Anderson JA, Weiss JL, et al. Air/liquid corneal organ culture: a light microscopic study[J]. Curr Eye Res, 1991, 10(8):739-749. doi:10.3109/02713689109013868.
[46] Harman RM, Bussche L, Ledbetter EC, et al. Establishment and characterization of an air-liquid canine corneal organ culture model to study acute Herpes keratitis[J]. J Virol, 2014, 88(23):13669-13677. doi:10.1128/JVI.02135-14.
[47] 王宇静, 杨燕宁. 人角膜上皮细胞体外培养的研究进展[J]. 眼科新进展, 2017,37(4):384-387,391. doi:10.13389/j.cnki.rao.2017.0098. WANG Yujing, YANG Yanning. Research advances in cultured human corneal epithelium cells in vitro[J]. Recent Adv Ophthalmol, 2017, 37(4):384-387,391. doi:10.13389/j.cnki.rao.2017.0098.
[48] 曲建秋. 甘露糖结合凝集素与Dectin-1、TLR2在真菌性角膜炎中的相互作用[D]. 青岛: 青岛大学, 2015.
[49] Wei C, Zhu MF, Petroll WM, et al. Pseudomonas aeruginosa infectious keratitis in a high oxygen transmissible rigid contact lens rabbit model[J]. Invest Ophthalmol Vis Sci, 2014, 55(9):5890-5899. doi:10.1167/iovs.14-14235.
[50] Chucair-Elliott AJ, Zheng M, Carr DJ. Degeneration and regeneration of corneal nerves in response to HSV-1 infection[J]. Invest Ophthalmol Vis Sci, 2015, 56(2):1097-1107. doi:10.1167/iovs.14-15596.
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