山东大学耳鼻喉眼学报 ›› 2023, Vol. 37 ›› Issue (2): 151-158.doi: 10.6040/j.issn.1673-3770.0.2021.536

• 综述 • 上一篇    

炎症因子在圆锥角膜中的研究进展

李孟婷,何书喜,王华   

  1. 湖南师范大学附属第一医院/湖南省人民医院 眼视光中心, 湖南 长沙 410005;
  • 发布日期:2023-03-30
  • 基金资助:
    湖南创新型省份建设项目专项任务书(2020SK218);湖南省人民医院院内项目(RS201614)

Research progress of inflammatory factors in Keratoconus

LI Mengting, HE Shuxi, WANG Hua   

  1. The Optometry Center, The First Affiliated Hospital of Hunan Normal University/Hunan Provincial People's Hospital, Changsha 410005, Hunan, China
  • Published:2023-03-30

摘要: 圆锥角膜(KC)是一种进行性的角膜扩张性疾病,常常导致近视加重、散光增加。圆锥角膜的病理生理机制尚不完全清楚,除遗传因素外,近年来有很多关于KC和炎症性因素的研究。有研究表明在KC患者的泪液中发现有可检测水平的炎症因子与蛋白酶,其中发现KC患者泪液的白细胞介素-6、肿瘤坏死因子-α和基质金属蛋白酶-9水平升高,且升高的水平与KC的病程发展呈正相关。除此之外,一些外界因素可以通过某些行为间接导致炎症的加重,从而加速KC的发生发展,比如揉眼、过敏反应等。病理性揉眼会使角膜形态发生变化,同时改变角膜环境,导致角膜间接性损伤。过敏反应中的免疫球蛋白E则是KC的潜在炎症分子。论文从炎症因子的来源、导致KC的途径进行综述。

关键词: 圆锥角膜, 炎症因子, 氧化应激, 过敏, 病理机制

Abstract: Keratoconus(KC)is a progressive corneal dilation disease, which aggravates myopia and astigmatism. The pathophysiological mechanism of KC remains vague. The role of genetic and inflammatory factors on KC has been investigated by previous studies. Detectable levels of inflammatory factors and proteases were found in the tears of patients with KC. Interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-9 were found in the tears of patients with KC. A higher level was positively correlated with the clinical course of KC. In addition, some external factors can indirectly lead to the aggravation of inflammation through certain behaviors, thus accelerating the occurrence and development of KC, such as eye rubbing, allergic reaction, etc. Pathological eye rubbing will change the corneal morphology, change the corneal environment, and cause indirect corneal injury. Immunoglobulin E in allergic reaction is the potential inflammatory molecule of KC. This paper aimed to review previous studies on inflammatory factors and the pathways leading to KC.

Key words: Keratoconus, Inflammatory factor, Oxidative stress, Allergic, Pathological mechanism

中图分类号: 

  • R772.2
[1] Shetty R, D'Souza S, Khamar P, et al. Biochemical markers and alterations in keratoconus[J]. Asia Pac J Ophthalmol(hpila), 2020, 9(6): 533-540. doi:10.1097/apo.0000000000000332
[2] Saghizadeh M, Chwa M, Aoki A, et al. Altered expression of growth factors and cytokines in keratoconus, bullous keratopathy and diabetic human corneas[J]. Exp Eye Res, 2001, 73(2): 179-189. doi:10.1006/exer.2001.1028
[3] Lema I, Durán JA, Ruiz C, et al. Inflammatory response to contact lenses in patients with keratoconus compared with myopic subjects[J]. Cornea, 2008, 27(7): 758-763. doi:10.1097/ICO.0b013e31816a3591
[4] Balasubramanian SA, Mohan S, Pye DC, et al. Proteases, proteolysis and inflammatory molecules in the tears of people with keratoconus[J]. Acta Ophthalmol, 2012, 90(4): e303-e309. doi:10.1111/j.1755-3768.2011.02369.x
[5] Kolozsvári BL, Berta A, Petrovski G, et al. Alterations of tear mediators in patients with keratoconus after corneal crosslinking associate with corneal changes[J]. PLoS One, 2013, 8(10): e76333. doi:10.1371/journal.pone.0076333
[6] Yabuta C, Yano F, Fujii A, et al. Galectin-3 enhances epithelial cell adhesion and wound healing in rat cornea[J]. Ophthalmic Res, 2014, 51(2): 96-103. doi:10.1159/000355846
[7] McMonnies CW. Inflammation and keratoconus[J]. Optom Vis Sci, 2015, 92(2): e35-e41. doi:10.1097/opx.0000000000000455
[8] Wilson SE, He YG, Weng J, et al. Epithelial injury induces keratocyte apoptosis: hypothesized role for the interleukin-1 system in the modulation of corneal tissue organization and wound healing[J]. Exp Eye Res, 1996, 62(4): 325-327. doi:10.1006/exer.1996.0038
[9] Balasubramanian SA, Pye DC, Willcox MD. Are proteinases the reason for keratoconus? [J]. Curr Eye Res, 2010, 35(3): 185-191. doi:10.3109/02713680903477824
[10] Abu-Amero KK, Azad TA, Kalantan H, et al. Mitochondrial sequence changes in keratoconus patients[J]. Invest Ophthalmol Vis Sci, 2014, 55(3): 1706-1710. doi:10.1167/iovs.14-13938
[11] Nabil KM, Elhady GM, Morsy H. The association between interleukin 1 beta promoter polymorphisms and keratoconus incidence and severity in an Egyptian population[J]. Clin Ophthalmol, 2019, 13: 2217-2223. doi:10.2147/OPTH.S220723
[12] Balasubramanian SA, Pye DC, Willcox MDP. Effects of eye rubbing on the levels of protease, protease activity and cytokines in tears: relevance in keratoconus[J]. Clin Exp Optom, 2013, 96(2): 214-218. doi:10.1111/cxo.12038
[13] Ebihara N, Matsuda A, Nakamura S, et al. Role of the IL-6 classic- and trans-signaling pathways in corneal sterile inflammation and wound healing[J]. Invest Ophthalmol Vis Sci, 2011, 52(12): 8549-8557. doi:10.1167/iovs.11-7956
[14] Jones SA, Horiuchi S, Topley N, et al. The soluble interleukin 6 receptor: mechanisms of production and implications in disease[J]. FASEB J, 2001, 15(1): 43-58. doi:10.1096/fj.99-1003rev
[15] Huovila APJ, Turner AJ, Pelto-Huikko M, et al. Shedding light on ADAM metalloproteinases[J]. Trends Biochem Sci, 2005, 30(7): 413-422. doi:10.1016/j.tibs.2005.05.006
[16] Izumi-Nagai K, Nagai N, Ozawa Y, et al. Interleukin-6 receptor-mediated activation of signal transducer and activator of transcription-3(STAT3)promotes choroidal neovascularization[J]. Am J Pathol, 2007, 170(6): 2149-2158. doi:10.2353/ajpath.2007.061018
[17] Abraham LJ, Kroeger KM. Impact of the-308 TNF promoter polymorphism on the transcriptional regulation of the TNF gene: relevance to disease[J]. J Leukoc Biol, 1999, 66(4): 562-566. doi:10.1002/jlb.66.4.562
[18] Arbab M, Tahir S, Niazi MK, et al. TNF-α genetic predisposition and higher expression of inflammatory pathway components in keratoconus[J]. Invest Ophthalmol Vis Sci, 2017, 58(9): 3481-3487. doi:10.1167/iovs.16-21400
[19] Beyaert R, Fiers W. Molecular mechanisms of tumor necrosis factor-induced cytotoxicity. What we do understand and what we do not[J]. FEBS Lett, 1994, 340(1/2): 9-16. doi:10.1016/0014-5793(94)80163-0
[20] Shetty R, Ghosh A, Lim RR, et al. Elevated expression of matrix metalloproteinase-9 and inflammatory cytokines in keratoconus patients is inhibited by cyclosporine A[J]. Invest Ophthalmol Vis Sci, 2015, 56(2): 738-750. doi:10.1167/iovs.14-14831
[21] Amento EP, Beck LS. TGF-beta and wound healing[J]. Ciba Found Symp, 1991, 157:115-123. doi:10.1002/9780470514061.ch8
[22] Saika S. TGF-β pathobiology in the eye[J]. Laboratory investigation, 2006, 86(2):106-115. doi: 10.1038/labinvest.3700375
[23] Sanford LP, Ormsby I, Gittenberger-de Groot AC, et al. TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes[J]. Development, 1997, 124(13): 2659-2670. doi:10.1242/dev.124.13.2659
[24] Priyadarsini S, McKay TB, Sarker-Nag A, et al. Keratoconus in vitro and the key players of the TGF-β pathway[J]. Mol Vis, 2015, 21: 577-588
[25] Engler C, Chakravarti S, Doyle J, et al. Transforming growth factor-β signaling pathway activation in Keratoconus[J]. Am J Ophthalmol, 2011, 151(5): 752-759.e2. doi:10.1016/j.ajo.2010.11.008
[26] Al Qattan A, Lessard L, Philip A, et al. Abstract 84: nAG(a salamander-derived protein)as an inhibitor of TGF-β signaling and fibrotic responses. PSRC 2018 Abstract supplement, 2018: 67-68. doi: 10.1097/01.GOX.0000533949.54354.9b
[27] Lyon D', McKay TB, Sarkar-Nag A, et al. Human keratoconus cell contractility is mediated by transforming growth factor-beta isoforms[J]. J Funct Biomater, 2015, 6(2): 422-438. doi:10.3390/jfb6020422
[28] Yang YN, Wang F, Zhou W, et al. TNF-α stimulates MMP-2 and MMP-9 activities in human corneal epithelial cells via the activation of FAK/ERK signaling[J]. Ophthalmic Res, 2012, 48(4): 165-170. doi:10.1159/000338819
[29] Aren A, Gökçe AH, Gökçe FS, et al. Roles of matrix metalloproteinases in the etiology of inguinal hernia[J]. Hernia, 2011, 15(6): 667-671. doi:10.1007/s10029-011-0846-5
[30] Nagase H, Woessner JF Jr. Matrix metalloproteinases[J]. J Biol Chem, 1999, 274(31): 21491-21494. doi:10.1074/jbc.274.31.21491
[31] Fini ME, Cook JR, Mohan R. Proteolytic mechanisms in corneal ulceration and repair[J]. Arch Dermatol Res, 1998, 290: S12-S23. doi:10.1007/pl00007449
[32] Du G, Liu C, Li X, et al. Induction of matrix metalloproteinase-1 by tumor necrosis factor-α is mediated by interleukin-6 in cultured fibroblasts of keratoconus[J]. Exp Biol(Med Maywood), 2016, 241(18): 2033-2041. doi:10.1177/1535370216650940
[33] Librach CL, Feigenbaum SL, Bass KE, et al. Interleukin-1 beta regulates human cytotrophoblast metalloproteinase activity and invasion in vitro[J]. J Biol Chem, 1994, 269(25): 17125-17131. doi:10.1016/S0021-9258(17)32529-2
[34] Vettraino IM, Roby J, Tolley T, et al. Collagenase-I, stromelysin-I, and matrilysin are expressed within the placenta during multiple stages of human pregnancy[J]. Placenta, 1996, 17(8): 557-563. doi:10.1016/s0143-4004(96)80072-5
[35] Li DQ, Lokeshwar BL, Solomon A, et al. Regulation of MMP-9 production by human corneal epithelial cells[J]. Exp Eye Res, 2001, 73(4): 449-459. doi:10.1006/exer.2001.1054
[36] Golub LM, Ramamurthy NS, McNamara TF, et al. Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs[J]. Crit Rev Oral Biol Med, 1991, 2(3): 297-321. doi:10.1177/10454411910020030201
[37] Peng SX, VonBargen EC, Bornes DM, et al. Permeability of articular cartilage to matrix metalloprotease inhibitors[J]. Pharm Res, 1998, 15(9): 1414-1418. doi:10.1023/a: 1011905806123
[38] Cox SW, Eley BM, Kiili M, et al. Collagen degradation by interleukin-1beta-stimulated gingival fibroblasts is accompanied by release and activation of multiple matrix metalloproteinases and cysteine proteinases[J]. Oral Dis, 2006, 12(1): 34-40. doi:10.1111/j.1601-0825.2005.01153.x
[39] di Martino E, Ali M, Inglehearn CF. Matrix metalloproteinases in keratoconus-Too much of a good thing? [J]. Exp Eye Res, 2019, 182: 137-143. doi:10.1016/j.exer.2019.03.016
[40] Smith VA, Easty DL. Matrix metalloproteinase 2: involvement in keratoconus[J]. Eur J Ophthalmol, 2000, 10(3): 215-226. doi:10.1177/112067210001000305
[41] Kenney MC, Chwa M, Opbroek AJ, et al. Increased gelatinolytic activity in keratoconus keratocyte cultures. A correlation to an altered matrix metalloproteinase-2/tissue inhibitor of metalloproteinase ratio[J]. Cornea, 1994, 13(2): 114-124. doi:10.1097/00003226-199403000-00003
[42] Stuart KA, Riordan SM, Lidder S, et al. Hepatocyte growth factor/scatter factor-induced intracellular signalling[J]. Int J Exp Pathol, 2000, 81(1): 17-30. doi:10.1046/j.1365-2613.2000.00138.x
[43] Organ SL, Tsao MS. An overview of the c-MET signaling pathway[J]. Ther Adv Med Oncol, 2011, 3(1): S7-S19. doi:10.1177/1758834011422556
[44] Wilson SE, Walker JW, Chwang EL, et al. Hepatocyte growth factor, keratinocyte growth factor, their receptors, fibroblast growth factor receptor-2, and the cells of the cornea[J]. Invest Ophthalmol Vis Sci, 1993, 34(8): 2544-2561. doi: 10.1007/BF00919654
[45] Wilson SE, Liang Q, Kim WJ. Lacrimal gland HGF, KGF, and EGF mRNA levels increase after corneal epithelial wounding[J]. Invest Ophthalmol Vis Sci, 1999, 40(10): 2185-2190. doi: doi:10.1097/00004397-199903940-00012
[46] Burdon KP, Macgregor S, Bykhovskaya Y, et al. Association of polymorphisms in the hepatocyte growth factor gene promoter with keratoconus[J]. Invest Ophthalmol Vis Sci, 2011, 52(11): 8514-8519. doi:10.1167/iovs.11-8261
[47] Liu Y, Michalopoulos GK, Zarnegar R. Structural and functional characterization of the mouse hepatocyte growth factor gene promoter[J]. J Biol Chem, 1994, 269(6): 4152-4160. doi: 10.1016/0092-8674(94)90120-1
[48] De Benedetto A, Agnihothri R, McGirt LY, et al. Atopic dermatitis: a disease caused by innate immune defects? [J]. J Invest Dermatol, 2009, 129(1): 14-30. doi:10.1038/jid.2008.259
[49] Kallinikos P, Efron N. On the etiology of keratocyte loss during contact lens wear[J]. Invest Ophthalmol Vis Sci, 2004, 45(9): 3011-3020. doi:10.1167/iovs.04-0129
[50] Shneor E, Millodot M, Blumberg S, et al. Characteristics of 244 patients with keratoconus seen in an optometric contact lens practice[J]. Clin Exp Optom, 2013, 96(2): 219-224. doi:10.1111/cxo.12005
[51] Winkler M, Shoa G, Xie Y, et al. Three-dimensional distribution of transverse collagen fibers in the anterior human corneal stroma[J]. Invest Ophthalmol Vis Sci, 2013, 54(12): 7293-7301. doi:10.1167/iovs.13-13150
[52] Mackiewicz Z, Määtä M, Stenman M, et al. Collagenolytic proteinases in keratoconus[J]. Cornea, 2006, 25(5): 603-610. doi:10.1097/01.ico.0000208820.32614.00.
[53] Fodor M, Kolozsvári BL, Petrovski G, et al. Effect of contact lens wear on the release of tear mediators in keratoconus[J]. Eye Contact Lens, 2013, 39(2): 147-152. doi:10.1097/ICL.0b013e318273b35f
[54] Shoham A, Hadziahmetovic M, Dunaief JL, et al. Oxidative stress in diseases of the human cornea[J]. Free Radic Biol Med, 2008, 45(8): 1047-1055. doi:10.1016/j.freeradbiomed.2008.07.021
[55] Kenney MC, Brown DJ. The cascade hypothesis of keratoconus[J]. Contact Lens Anterior Eye, 2003, 26(3): 139-146. doi:10.1016/S1367-0484(03)00022-5
[56] Wojcik K A, Kaminska A, Blasiak J, et al. Oxidative stress in the pathogenesis of keratoconus and fuchs endothelial corneal dystrophy[J]. Int J Mol Sci, 2013, 14(9): 19294-19308. doi:10.3390/ijms140919294
[57] Gondhowiardjo TD, van Haeringen NJ, Völker-Dieben HJ, et al. Analysis of corneal aldehyde dehydrogenase patterns in pathologic corneas[J]. Cornea, 1993, 12(2): 146-154. doi:10.1097/00003226-199303000-00010
[58] Sharma N, Rao K, Maharana PK, et al. Ocular allergy and keratoconus[J]. Indian J Ophthalmol, 2013, 61(8): 407-409. doi:10.4103/0301-4738.116063
[59] Ahuja P, Dadachanji Z, Shetty R, et al. Relevance of IgE, allergy and eye rubbing in the pathogenesis and management of Keratoconus[J]. Indian J Ophthalmol, 2020, 68(10): 2067-2074. doi:10.4103/ijo.IJO_1191_19
[60] 夏艳云, 钟定娟, 王华, 等. 高能量加速型角膜胶原交联术对圆锥角膜眼表的影响[J]. 山东大学耳鼻喉眼学报, 2021, 35(6): 42-51. doi: 10.6040/j.issn.1673-3770.0.2021.432 XIA Yanyun, ZHONG Dingjuan, WANG Hua, et al. Effect of high-energy accelerated corneal collagen cross-linking on the ocular surface of keratoconus[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2021, 35(6): 42-51. doi: 10.6040/j.issn.1673-3770.0.2021.432
[1] 苏杰,杨馥宇,李猛,陈荟茹,蒋利生,王丽香. GLP-1诱导的自噬对糖尿病大鼠视网膜病变的保护作用[J]. 山东大学耳鼻喉眼学报, 2022, 36(5): 30-34.
[2] 王传玉,牟国营. 圆锥角膜合并K-F环1例并文献复习[J]. 山东大学耳鼻喉眼学报, 2022, 36(5): 58-62.
[3] 梁旭,史丽. 慢性鼻窦炎生物靶向药物治疗的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 30-35.
[4] 梁旭,金鹏,赵莉,于克娜,訾晓雪,袁光美,臧以冉,张勤勤,张海令,史丽,张红萍. 鼻呼出一氧化氮对慢性鼻窦炎诊断的临床应用价值[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 181-188.
[5] 张雅琪,刘慧敏,曹淋曼,王子钰,林旭,李燕萍,薛刚,吴靖芳. MAPK、PI3K-AKT、NF-κB在小鼠过敏性鼻炎中的表达及意义[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 254-259.
[6] 金霄雪,韩莹莹,郭瑞祥,倪守洁,邹娟娟,王岩,李延忠. 替牙期扁桃体伴腺样体肥大患儿过敏因素与颌面畸形的相关性[J]. 山东大学耳鼻喉眼学报, 2022, 36(2): 45-50.
[7] 张依,王文俊,杨安怀. SIRT1激动剂白藜芦醇在眼部疾病中的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(2): 151-156.
[8] 庞冲,边赛男,张冰,尹旭,陆颖霞,叶鹏飞,王湛,赵晶,高彦,关凯. 儿童过敏性鼻炎粉尘螨特异性舌下免疫治疗短期疗效评估[J]. 山东大学耳鼻喉眼学报, 2022, 36(1): 70-74.
[9] 黄天泽,陈迪,李莹. 机器学习在眼表疾病诊断及角膜手术中的应用进展[J]. 山东大学耳鼻喉眼学报, 2021, 35(6): 13-19.
[10] 夏艳云,钟定娟,王华,李孟婷,李前,陈蛟,何书喜. 高能量加速型角膜胶原交联术对圆锥角膜眼表的影响[J]. 山东大学耳鼻喉眼学报, 2021, 35(6): 42-51.
[11] 王鑫,刘巧平,闫占峰,刘思溟,朱雅静,丁倩,张莹,田媛,张京然. 基于网络药理学探究小青龙汤治疗过敏性鼻炎的作用机制[J]. 山东大学耳鼻喉眼学报, 2021, 35(5): 46-55.
[12] 王宇婷,王嘉玺. microRNA在过敏性鼻炎发病机制中的研究进展[J]. 山东大学耳鼻喉眼学报, 2021, 35(5): 98-104.
[13] 李化静,郝润梅,戴皓,张令,申震,权芳,邵渊. 儿茶素抑制卵清蛋白诱导的过敏性鼻炎小鼠模型炎症反应的机制研究[J]. 山东大学耳鼻喉眼学报, 2021, 35(4): 1-7.
[14] 付奕豪,徐逸轩,严宏,张婕. 谷氧还蛋白在眼病中的作用研究进展[J]. 山东大学耳鼻喉眼学报, 2021, 35(3): 125-130.
[15] 赵良慧,蔡涛,杜显丽. 圆锥角膜家系中ZEB1基因突变的致病性分析[J]. 山东大学耳鼻喉眼学报, 2021, 35(2): 98-104.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!