Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2022, Vol. 36 ›› Issue (2): 144-150.doi: 10.6040/j.issn.1673-3770.0.2020.484

Previous Articles     Next Articles

Research progress in the inflammatory reaction and anti-inflammatory treatments in dry eye

DI Yu,LI Ying   

  1. Department of Ophthalmology, Chinese Academy of Medical Sciences / Peking Union Medical College / Peking Union Medical College Hospital, Beijing 100730, China
  • Published:2022-04-15

PDF (PC)

408

Abstract: Dry eye is a multifactorial disease of the tear film and ocular surface. In recent years, it has become one of the most common ocular surface diseases, with its prevalence increasing every year. Inflammation plays a key role in the pathogenesis of dry eye. It can stimulate ocular surface cells, activate the local immune response, lead to unstable tear films, increase the osmolality of tears, and then cause local ocular surface damage. Multiple inflammatory mediators and immune cells participate in the development of dry eye. There is increasing research on the inflammatory reaction involved in dry eye, and this paper reviews the inflammatory mediators, immune cells, immune response, and anti-inflammatory treatments to systematically understand the inflammatory reaction mechanism of dry eye and its clinical significance.

Key words: Dry eye, Inflammatory mediator, Inflammatory reaction, Anti-inflammation, Treatment

CLC Number: 

  • R777.34
[1] Periman LM, Perez VL, Saban DR, et al. The immunological basis of dry eye disease and current topical treatment options[J]. J Ocul Pharmacol Ther, 2020, 36(3): 137-146. doi:10.1089/jop.2019.0060.
[2] Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II definition and classification report[J]. Ocul Surf, 2017, 15(3): 276-283. doi:10.1016/j.jtos.2017.05.008.
[3] Stern ME, Schaumburg CS, Pflugfelder SC. Dry eye as a mucosal autoimmune disease[J]. Int Rev Immunol, 2013, 32(1): 19-41. doi:10.3109/08830185.2012.748052.
[4] 孙子雯, 崔洪玮, 孙喜灵, 等. 干眼病的病因、发病机制及治疗进展[J]. 山东大学耳鼻喉眼学报, 2019, 3(33):159-166. doi: 10.6040/j.issn.1673-3770.0.2018.411. SUN Ziwen, CUI Hongwei, SUN Xiling, et al. Etiology, pathogenesis, and management of dry eye[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 3(33):159-166. doi: 10.6040/j.issn.1673-3770.0.2018.411.
[5] Yagci A, Gurdal C. The role and treatment of inflammation in dry eye disease[J]. Int Ophthalmol, 2014, 34(6): 1291-1301. doi:10.1007/s10792-014-9969-x.
[6] 高雅, 李冰, 陈研遐, 等. 白介素1β在干眼患者眼表的表达[J]. 中华眼视光学与视觉科学杂志, 2014, 16(4): 228-232. doi: 10.3760/cma.j.issn.1674-845X.2014.04.009. GAO Ya, LI Bing, CHEN Yanxia, et al. A study of the expression of IL-1 beta on the ocular surface in dry eye patients[J]. Chinese Journal of Optometry & Ophthalmology, 2014, 16(4): 228-232. doi: 10.3760/cma.j.issn.1674-845X.2014.04.009.
[7] Benitez J, Cantu-Dibildox J, Sanz-González SM, et al. Cytokine expression in tears of patients with Glaucoma or dry eye disease: a prospective, observational cohort study[J]. Eur J Ophthalmol, 2019, 29(4): 437-443. doi:10.1177/1120672118795399.
[8] Landsend ECS, Utheim A, Pedersen HR, et al. The level of inflammatory tear cytokines is elevated in congenital aniridia and associated with meibomian gland dysfunction[J]. Invest Ophthalmol Vis Sci, 2018, 59(5): 2197-2204. doi:10.1167/iovs.18-24027.
[9] Lee H, Chung B, Kim KS, et al. Effects of topical loteprednol etabonate on tear cytokines and clinical outcomes in moderate and severe meibomian gland dysfunction: randomized clinical trial[J]. Am J Ophthalmol, 2014, 158(6): 1172-1183.e1. doi:10.1016/j.ajo.2014.08.015.
[10] Bi Y, Yang R. Direct and indirect regulatory mechanisms in TH17 cell differentiation and functions[J]. Scand J Immunol, 2012, 75(6): 543-552. doi:10.1111/j.1365-3083.2012.02686.x.
[11] Higuchi A, Kawakita T, Tsubota K. IL-6 induction in desiccated corneal epithelium in vitro and in vivo[J]. Mol Vis, 2011, 17: 2400-2406. doi: 10.2214/ajr.142.6.1205.
[12] Na KS, Mok JW, Kim JY, et al. Correlations between tear cytokines, chemokines, and soluble receptors and clinical severity of dry eye disease[J]. Invest Ophthalmol Vis Sci, 2012, 53(9): 5443-5450. doi:10.1167/iovs.11-9417.
[13] McDonnell PJ, Pflugfelder SC, Stern ME, et al. Study design and baseline findings from the progression of ocular findings(PROOF)natural history study of dry eye[J]. BMC Ophthalmol, 2017, 17(1): 265. doi:10.1186/s12886-017-0646-5.
[14] Jung JW, Han SJ, Nam SM, et al. Meibomian gland dysfunction and tear cytokines after cataract surgery according to preoperative meibomian gland status[J]. Clin Exp Ophthalmol, 2016, 44(7): 555-562. doi:10.1111/ceo.12744.
[15] De Paiva CS, Chotikavanich S, Pangelinan SB, et al. IL-17 disrupts corneal barrier following desiccating stress[J]. Mucosal Immunol, 2009, 2(3): 243-253. doi:10.1038/mi.2009.5.
[16] Chen Y, Chauhan SK, Lee HS, et al. Chronic dry eye disease is principally mediated by effector memory Th17 cells[J]. Mucosal Immunol, 2014, 7(1): 38-45. doi:10.1038/mi.2013.20.
[17] Lee SY, Han SJ, Nam SM, et al. Analysis of tear cytokines and clinical correlations in sjögren syndrome dry eye patients and non-sjögren syndrome dry eye patients[J]. Am J Ophthalmol, 2013, 156(2): 247-253. doi:10.1016/j.ajo.2013.04.003.
[18] Mrugacz M, Ostrowska L, Bryl A, et al. Pro-inflammatory cytokines associated with clinical severity of dry eye disease of patients with depression[J]. Adv Med Sci, 2017, 62(2): 338-344. doi:10.1016/j.advms.2017.03.003.
[19] Tong L, Beuerman R, Simonyi S, et al. Effects of punctal occlusion on clinical signs and symptoms and on tear cytokine levels in patients with dry eye[J]. Ocul Surf, 2016, 14(2): 233-241. doi:10.1016/j.jtos.2015.12.004.
[20] Pflugfelder SC, De Paiva CS, Moore QL, et al. Aqueous tear deficiency increases conjunctival interferon-γ(IFN-γ)expression and goblet cell loss[J]. Invest Ophthalmol Vis Sci, 2015, 56(12): 7545-7550. doi:10.1167/iovs.15-17627.
[21] Jackson DC, Zeng W, Wong CY, et al. Tear interferon-gamma as a biomarker for evaporative dry eye disease[J]. Invest Ophthalmol Vis Sci, 2016, 57(11): 4824-4830. doi:10.1167/iovs.16-19757.
[22] Chotikavanich S, de Paiva CS, Li DQ, et al. Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome[J]. Invest Ophthalmol Vis Sci, 2009, 50(7): 3203-3209. doi:10.1167/iovs.08-2476.
[23] Yang S, Lee HJ, Kim DY, et al. The use of conjunctival staining to measure ocular surface inflammation in patients with dry eye[J]. Cornea, 2019, 38(6): 698-705. doi:10.1097/ico.0000000000001916.
[24] Messmer EM, von Lindenfels V, Garbe A, et al. Matrix metalloproteinase 9 testing in dry eye disease using a commercially available point-of-care immunoassay[J]. Ophthalmology, 2016, 123(11): 2300-2308. doi:10.1016/j.ophtha.2016.07.028.
[25] Schargus M, Ivanova S, Kakkassery V, et al. Correlation of tear film osmolarity and 2 different MMP-9 tests with common dry eye tests in a cohort of non-dry eye patients[J]. Cornea, 2015, 34(7): 739-744. doi:10.1097/ico.0000000000000449.
[26] Enríquez-de-Salamanca A, Castellanos E, Stern ME, et al. Tear cytokine and chemokine analysis and clinical correlations in evaporative-type dry eye disease[J]. Mol Vis, 2010, 16: 862-873. PMID: 20508732.
[27] Massingale ML, Li XH, Vallabhajosyula M, et al. Analysis of inflammatory cytokines in the tears of dry eye patients[J]. Cornea, 2009, 28(9): 1023-1027. doi:10.1097/ico.0b013e3181a16578.
[28] Choi W, Li ZR, Oh HJ, et al. Expression of CCR5 and its ligands CCL3, -4, and -5 in the tear film and ocular surface of patients with dry eye disease[J]. Curr Eye Res, 2012, 37(1): 12-17. doi:10.3109/02713683.2011.622852.
[29] Nicolle P, Liang H, Reboussin E, et al. Proinflammatory markers, chemokines, and enkephalin in patients suffering from dry eye disease[J]. Int J Mol Sci, 2018, 19(4): 1221. doi:10.3390/ijms19041221.
[30] Wang T, Li WH, Cheng HH, et al. The important role of the chemokine axis CCR7-CCL19 and CCR7-CCL21 in the pathophysiology of the immuno-inflammatory response in dry eye disease[J]. Ocular Immunol Inflamm, 2019: 1-12. doi:10.1080/09273948.2019.1674891.
[31] Lefort CT, Ley K. Neutrophil arrest by LFA-1 activation[J]. Front Immunol, 2012, 3: 157. doi:10.3389/fimmu.2012.00157.
[32] Hogg N, Laschinger M, Giles K, et al. T-cell integrins: more than just sticking points[J]. J Cell Sci, 2003, 116(Pt 23): 4695-4705. doi:10.1242/jcs.00876.
[33] Liu M, Gao H, Wang T, et al. An essential role for dendritic cells in vernal keratoconjunctivitis: analysis by laser scanning confocal microscopy[J]. Clin Exp Allergy, 2014, 44(3): 362-370. doi:10.1111/cea.12264.
[34] Hamrah P, Huq SO, Liu Y, et al. Corneal immunity is mediated by heterogeneous population of antigen-presenting cells[J]. J Leukoc Biol, 2003, 74(2): 172-178. doi:10.1189/jlb.1102544.
[35] El Annan J, Chauhan SK, Ecoiffier T, et al. Characterization of effector T cells in dry eye disease[J]. Invest Ophthalmol Vis Sci, 2009, 50(8): 3802-3807. doi:10.1167/iovs.08-2417.
[36] De Paiva CS, Villarreal AL, Corrales RM, et al. Dry eye-induced conjunctival epithelial squamous Metaplasia is modulated by interferon-gamma[J]. Invest Ophthalmol Vis Sci, 2007, 48(6): 2553-2560. doi:10.1167/iovs.07-0069.
[37] Chauhan SK, El Annan J, Ecoiffier T, et al. Autoimmunity in dry eye is due to resistance of Th17 to Treg suppression[J]. J Immunol, 2009, 182(3): 1247-1252. doi:10.4049/jimmunol.182.3.1247.
[38] von Knethen A, Heinicke U, Weigert A, et al. Histone deacetylation inhibitors as modulators of regulatory T cells[J]. Int J Mol Sci, 2020, 21(7): 2356. doi:10.3390/ijms21072356.
[39] Ratay ML, Balmert SC, Bassin EJ, et al. Controlled release of an HDAC inhibitor for reduction of inflammation in dry eye disease[J]. Acta Biomater, 2018, 71: 261-270. doi:10.1016/j.actbio.2018.03.002.
[40] 蔡丽萍, 张宏. 炎症免疫相关信号通路在干眼发病机制中的研究进展[J]. 国际眼科杂志, 2016, 16(6): 1084-1088. doi:10.3980/j.issn.1672-5123.2016.6.20. LIPING Cai, HONG Zhang. Research progress on inflammatory immunity related signaling pathway for the pathogenesis of dry eye[J]. Int Eye Sci, 2016, 16(6): 1084-1088. doi:10.3980/j.issn.1672-5123.2016.6.20.
[41] Hattori T, Takahashi H, Dana R. Novel insights into the immunoregulatory function and localization of dendritic cells[J]. Cornea, 2016, 35(Suppl 1): S49-S54. doi:10.1097/ico.0000000000001005.
[42] Pflugfelder SC, Corrales RM, de Paiva CS. T helper cytokines in dry eye disease[J]. Exp Eye Res, 2013, 117: 118-125. doi:10.1016/j.exer.2013.08.013.
[43] Pflugfelder SC, Geerling G, Kinoshita S, et al. Management and therapy of dry eye disease: Report of the management and therapy subcommittee of the international Dry Eye WorkShop(2007)[C] //2007, 5: 163-178.
[44] Pinto-Fraga J, Lopez-Miguel A, Gonzalez-Garcia MJ, et al. Topical fluorometholone protects the ocular surface of dry eye patients from desiccating stress: a randomized controlled clinical trial[J]. Ophthalmology, 2016, 123(1):141-53. doi: 10.1016/j.ophtha.2015.09.029.
[45] Jung HH, Ji YS, Sung MS, et al. Long-term outcome of treatment with topical corticosteroids for severe dry eye associated with sjögren's syndrome[J]. Chonnam Med J, 2015, 51(1): 26-32. doi:10.4068/cmj.2015.51.1.26.
[46] Sall K, Stevenson OD, Mundorf TK, et al. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease[J]. Ophthalmology, 2000, 107(4): 631-639. doi:10.1016/S0161-6420(99)00176-1.
[47] Ji YW, Kim HM, Ryu SY, et al. Changes in human tear proteome following topical treatment of dry eye disease: cyclosporine A versus diquafosol tetrasodium[J]. Invest Ophthalmol Vis Sci, 2019, 60(15): 5035-5044. doi:10.1167/iovs.19-27872.
[48] Daull P, Barabino S, Feraille L, et al. Modulation of inflammation-related genes in the cornea of a mouse model of dry eye upon treatment with cyclosporine eye drops[J]. Curr Eye Res, 2019, 44(5): 476-485. doi:10.1080/02713683.2018.1563197.
[49] Guimaraes de Souza R, Yu Z, Stern ME, et al. Suppression of Th1-mediated keratoconjunctivitis sicca by lifitegrast[J]. J Ocul Pharmacol Ther, 2018, 34(7): 543-549. doi:10.1089/jop.2018.0047.
[50] Haber SL, Benson V, Buckway CJ, et al. Lifitegrast: a novel drug for patients with dry eye disease[J]. Ther Adv Ophthalmol, 2019, 11: 2515841419870366. doi:10.1177/2515841419870366.
[51] Semba CP, Torkildsen GL, Lonsdale JD, et al. A phase 2 randomized, double-masked, placebo-controlled study of a novel integrin antagonist(SAR 1118)for the treatment of dry eye[J]. Am J Ophthalmol, 2012, 153(6): 1050-1060.e1. doi:10.1016/j.ajo.2011.11.003.
[52] Holland EJ, Luchs J, Karpecki PM, et al. Lifitegrast for the treatment of dry eye disease: results of a phase Ⅲ, randomized, double-masked, placebo-controlled trial(OPUS-3)[J]. Ophthalmology, 2017, 124(1): 53-60. doi:10.1016/j.ophtha.2016.09.025.
[53] Kim CE, Kleinman HK, Sosne G, et al. RGN-259(thymosin β4)improves clinically important dry eye efficacies in comparison with prescription drugs in a dry eye model[J]. Sci Rep, 2018, 8(1): 1-14. doi:10.1038/s41598-018-28861-5.
[54] Sosne G, Dunn SP, Kim C. Thymosin β4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial[J]. Cornea, 2015, 34(5): 491-496. doi:10.1097/ico.0000000000000379.
[1] ZHANG YuOverview,QU YiGuidance. Research progress on the pathogenesis and control of ocular toxoplasmosis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(5): 70-76.
[2] SONG QingOverview,SONG XichengGuidance. Research progress of anlotinib combination therapy in cancer treatment [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(5): 106-112.
[3] ZHANG Keren, LEI Chunyan, ZHANG Meixia. Floppy eyelid syndrome associated with obstructive sleep apnea: a case report [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(5): 125-128.
[4] SHI Anni, ZHANG Jiajia, BAI Peng, ZHANG Chongyang. Analysis of a therapeutic modality for sudden deafness utilizing neck acupuncture comprising seven lines of treatment [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(4): 103-107.
[5] XIONG Panhui, SHEN Yang,YANG Yucheng. Advancements in the diagnosis and treatment of chronic sinusitis based on phenotypes and endotypes [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(3): 15-19.
[6] LIANG Xu,SHI Li. Research progress in biologic targeted drug therapy for chronic sinusitis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(3): 30-35.
[7] GU Yu, WAN Xin,XIAO Zi'an. The interaction between neutrophils and eosinophils in chronic rhinosinusitis and the implications on treatment options [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(3): 56-63.
[8] ZENG Xianting, WANG Guangke, SUN Zhanwei, WU Tianyi, LI Shichao, WANG Weiwei. Postoperative efficacy of proton pump inhibitor in the treatment of difficult-to-treat rhinosinusitis with laryngopharyngeal reflux [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(3): 189-194.
[9] ZHANG Taoran, WANG Wei, LI Mingming, HUANG Yingxiang. Subfoveal choroidal thickness changes following intravitreal ranibizumab treatment in choroidal neovascularization due to pathological myopia [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(2): 68-71.
[10] BAI Lingling, WANG Hongxing, WANG Lichun. Effect of absorbable lacrimal plug combined with artificial tears on the treatment of moderate to severe dry eye and its impact on vision-related quality of life [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(2): 78-82.
[11] HUA Hongli, LI Song,TAO Zezhang. Research progress of artificial intelligence in the diagnosis and treatment of nasopharyngeal carcinoma [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(2): 113-119.
[12] CHEN Kun, LU Hui, HUANG Qi, LI Lei, MENG Guozhen, YANG Jun, HOU Dongming. Clinical diagnosis and treatment of congenital nasal sinus mass in children [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(1): 81-85.
[13] ZENG Bin, LÜ Dan, REN Jia, HU Juanjuan, YU Lingyu, LU Huan, YANG Hui. Application of laryngeal microsurgery in severe neonatal upper airway obstruction [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(1): 95-99.
[14] ZHAO Xinghe, FAN Mingyue, DOU Xunwu, JIA Guangbiao. Primary large B-cell lymphoma of tonsil in children: a case report and document review [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(1): 120-124.
[15] LU Xiaoyan, WEN Shuxin. Advances in the treatment of congenital choanal atresia [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(1): 138-142.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] HE Shou-huan,CHEN Bin,YIN Shan-kai,SU Kai-ming,JIANG Xiao . Morphological changes of the upper airway in OSAHS patients with UPPP
[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2008, 22(5): 385 -388 .
[2] SONG Xi-cheng,ZHANG Qing-quan,XIA Yong-hong,LIU Lu-yi, YU Lu-xin,WANG Gao,JIANG Xiu-liang . Post-operative ICU monitoring and nursing for patients with OSAHS[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2008, 22(5): 389 -392 .
[3] XUE Wei-guo,SUN Jie,JIN Zheng,SHI Wen-bin,XIN Lu,LIN Guo-Jing,LI Jia-yun . [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(4): 300 -303 .
[4] ZHANG Qing-quan,LI Xin-min,WANG Qiang,WANG Yong-fu . Some experience of the endoscopy treatment of maxillary sinus lesion with the canine tooth fossa approach[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2007, 21(1): 38 -39 .
[5] DONG Pin,LI Xiao-yan,TU Li-qiang,MENG Qing-hong,WANG Sang,XIE Jin,JIANG Yan . Reconstruction for advanced hypopharyngeal carcinoma and laryngeal recurrent carcinoma[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2007, 21(5): 385 -387 .
[6] JIANG Shao-hong,ZHU Yu-hong,WANG Qiang,SONG Xi-cheng . Intractable primary epistaxis: a report of 101 cases[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2007, 21(6): 542 -544 .
[7] . [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2008, 22(1): 74 -77 .
[8] LEIXun, LIU Qianghe, KONG Zhongyu, XIANG Qiu, GENG WANping, HUANG Hui, DONG Yiyuan, LIU Fangxian. ARelationship between expression of Survivin and radiosensitization effect of EGCG in xenotransplanted nasopharyngeal carcinoma[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2009, 23(1): 6 -9 .
[9] . [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2009, 23(2): 73 -74 .
[10] . [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2010, 24(01): 29 -33 .
Website Copyright: Editorial Office of Journal of Otolaryngology and Ophthalmology of Shandong University
Address: No.27 Shanda South Road, Jinan, Shandong, China. Post code: 250100 Tel: +86-0531-88366912 Email: ebhxb@sdu.edu.cn Supported by Beijing Magtech Co.Ltd