山东大学耳鼻喉眼学报 ›› 2024, Vol. 38 ›› Issue (2): 163-168.doi: 10.6040/j.issn.1673-3770.0.2023.333
• 综述 • 上一篇
伦英俊1,陈晨2,高宏程2,范清琳3,邰仁清1
LUN Yingjun1, CHEN Chen2, GAO Hongcheng2, FAN Qinglin3, TAI Renqing1
摘要: 糖尿病视网膜病变(diabetic retinopathy, DR)是一种由糖尿病引起的微血管并发症,也是导致患者失明的首要原因。其发病机制受多种因素影响,例如免疫炎症、氧化应激、多元醇途径等。目前认为免疫炎症机制在DR的发生发展起重要作用。Toll样受体4(Toll-like receptor 4, TLR4)/核转录因子-κB(nuclear factor kappa B, NF-κB)通路是介导炎症因子释放的重要途径,在免疫炎性机制中发挥关键作用。目前不少研究证实抑制TLR4/NF-κB信号通路可有效减轻DR。本文就TLR4/NF-κB通道在DR中的作用进行综述,可为治疗DR提供新的靶点。
中图分类号:
[1] | Tan TE, Wong TY. Diabetic retinopathy: Looking forward to 2030[J]. Front Endocrinol(Lausanne), 2023,13: 1077669. doi:10.3389/fendo.2022.1077669 |
[2] | Teo ZL, Tham YC, Yu M, et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis[J]. Ophthalmology, 2021,128(11): 1580-1591. doi:10.1016/j.ophtha.2021.04.027 |
[3] | Yue T, Shi Y, Luo S, et al. The role of inflammation in immune system of diabetic retinopathy: molecular mechanisms, pathogenetic role and therapeutic implications[J]. Front Immunol, 2022, 13: 1055087. doi:10.3389/fimmu.2022.1055087 |
[4] | Wallsh JO, Gallemore RP. Anti-VEGF-resistant retinal diseases: a review of the latest treatment options[J]. Cells, 2021,10(5): 1049. doi:10.3390/cells10051049 |
[5] | Taurone S, Ralli M, Nebbioso M, et al. The role of inflammation in diabetic retinopathy: a review[J]. Eur Rev Med Pharmacol Sci, 2020, 24(20): 10319-10329. doi:10.26355/eurrev_202010_23379 |
[6] | Cvitkovic K, Sesar A, Sesar I, et al. Concentrations of selected cytokines and vascular endothelial growth factor in aqueous humor and serum of diabetic patients[J]. Semin Ophthalmol, 2020, 35(2): 126-133. doi:10.1080/08820538.2020.1755320 |
[7] | 王娇娇,李苗,宋宗明. 糖尿病视网膜病变的机制和细胞模型研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(5): 93-99. doi:10.6040/j.issn.1673-3770.0.2021.203 WANG Jiaojiao, LI Miao, SONG Zongming. Progress in diabetic retinopathy mechanisms and cellular models[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(5): 93-99. doi: 10.6040/j.issn.1673-3770.0.2021.203 |
[8] | Shu X, Hu Y, Huang C, et al. Nimbolide ameliorates the streptozotocin-induced diabetic retinopathy in rats through the inhibition of TLR4/NF-κB signaling pathway[J]. Saudi J Biol Sci, 2021, 28(8): 4255-4262. doi:10.1016/j.sjbs.2021.06.039 |
[9] | Dabi YT, Ajagbe AO, Degechisa ST. Toll-like receptors in pathogenesis of neurodegenerative diseases and their therapeutic potential[J]. Immun Inflamm Dis, 2023, 11(4): e839. doi:10.1002/iid3.839 |
[10] | Balka KR, De Nardo D. Understanding early TLR signaling through the myddosome[J]. J Leukoc Biol, 2019, 105(2): 339-351. doi:10.1002/JLB.MR0318-096R |
[11] | Romerio A, Peri F. Increasing the chemical variety of small-molecule-based TLR4 modulators: an overview[J]. Front Immunol, 2020, 11: 1210. doi:10.3389/fimmu.2020.01210 |
[12] | Wang L, Wang J, Fang JZ, et al. High glucose induces and activates Toll-like receptor 4 in endothelial cells of diabetic retinopathy[J]. Diabetol Metab Syndr, 2015, 7: 89. doi:10.1186/s13098-015-0086-4 |
[13] | 李晓洁, 许泽鹏, 黄玉婷, 等. Toll样受体4信号通路在糖尿病视网膜病变中的研究进展[J]. 中国中医眼科杂志, 2023, 33(1): 73-79. doi:10.13444/j.cnki.zgzyykzz.2023.01.019 LI Xiaojie, XU Zepeng, HUANG Yuting, et al. Research progress of Toll-like receptor 4 signaling pathway in diabetic retinopathy[J]. China Journal of Chinese Ophthalmology, 2023, 33(1): 73-79. doi:10.13444/j.cnki.zgzyykzz.2023.01.019 |
[14] | Jagtap P, Prasad P, Pateria A, et al. A single step in vitro bioassay mimicking TLR4-LPS pathway and the role of MD2 and CD14 coreceptors[J]. Front Immunol, 2020,11: 5. doi:10.3389/fimmu.2020.00005 |
[15] | Bayer AL, Alcaide P. MyD88: At the heart of inflammatory signaling and cardiovascular disease[J]. J Mol Cell Cardiol, 2021,161: 75-85. doi:10.1016/j.yjmcc.2021.08.001 |
[16] | Fitzgerald KA, Kagan JC. Toll-like receptors and the control of Immunity[J]. Cell, 2020,180(6): 1044-1066. doi:10.1016/j.cell.2020.02.041 |
[17] | Bayan N, Yazdanpanah N, Rezaei N. Role of toll-like receptor 4 in diabetic retinopathy[J]. Pharmacol Res, 2022, 175: 105960. doi:10.1016/j.phrs.2021.105960 |
[18] | Durand JK, Baldwin AS. Targeting IKK and NF-κB for therapy[J]. Adv Protein Chem Struct Biol, 2017, 107: 77-115. doi:10.1016/bs.apcsb.2016.11.006 |
[19] | Zhang Y, Li H, Wang C, et al. Toll like receptor 4 gene Asp299Gly polymorphism increases the risk of diabetic microvascular complications: a meta analysis[J]. Diabetol Metab Syndr, 2022, 14(1): 79. doi:10.1186/s13098-022-00849-2 |
[20] | Fu H, Liu H. Deletion of toll-like receptor 4 ameliorates diabetic retinopathy in mice[J]. Arch Physiol Biochem,2023, 129(2): 519-525. doi:10.1080/13813455.2020.1841795 |
[21] | Chen H, Yan T, Song Z, et al. MD2 blockade prevents modified LDL-induced retinal injury in diabetes by suppressing NADPH oxidase-4 interaction with Toll-like receptor-4[J]. Exp Mol Med, 2021, 53(4): 681-694. doi:10.1038/s12276-021-00607-w |
[22] | Mesquida M, Drawnel F, Lait PJ, et al. Modelling macular edema: the effect of IL-6 and IL-6R blockade on human blood-retinal barrier integrity in vitro[J]. Transl Vis Sci Technol,2019, 8(5): 32. doi:10.1167/tvst.8.5.32 |
[23] | Taghavi Y, Hassanshahi G, Kounis NG, et al. Monocyte chemoattractant protein-1(MCP-1/CCL2)in diabetic retinopathy: latest evidence and clinical considerations[J]. J Cell Commun Signal, 2019, 13(4): 451-462. doi: 10.1007/s12079-018-00500-8 |
[24] | O'leary F, Campbell M. The blood-retina barrier in health and disease[J]. FEBS J, 2023, 290(4): 878-891. doi:10.1111/febs.16330 |
[25] | Madore C, Yin ZR, Leibowitz J, et al. Microglia, lifestyle stress, and neurodegeneration[J]. Immunity, 2020, 52(2): 222-240. doi:10.1016/j.immuni.2019.12.003 |
[26] | Mcmenamin PG, Saban DR, Dando S J. Immune cells in the retina and choroid: two different tissue environments that require different defenses and surveillance[J]. Prog Retin Eye Res, 2019, 70: 85-98. doi:10.1016/j.preteyeres.2018.12.002 |
[27] | Altmann C, Schmidt MHH. The role of microglia in diabetic retinopathy: inflammation, microvasculature defects and neurodegeneration[J]. Int J Mol Sci, 2018, 19(1): 110. doi:10.3390/ijms19010110 |
[28] | Orihuela R, McPherson CA, Harry GJ. Microglial M1/M2 polarization and metabolic states[J]. Br J Pharmacol, 2016, 173(4): 649-665. doi:10.1111/bph.13139 |
[29] | Wang XL, Chen F, Shi H, et al. Oxymatrine inhibits neuroinflammation by regulating M1/M2 polarization in N9 microglia through the TLR4/NF-κB pathway[J]. Int Immunopharmacol, 2021, 100: 108139. doi:10.1016/j.intimp.2021.108139 |
[30] | Fang MY, Wan WC, Li QM, et al. Asiatic acid attenuates diabetic retinopathy through TLR4/MyD88/NF-κB p65 mediated modulation of microglia polarization[J]. Life Sci, 2021, 277: 119567. doi:10.1016/j.lfs.2021.119567 |
[31] | Gu C, Zhang HJ, Zhao SF, et al. Mesenchymal stem cell exosomal miR-146a mediates the regulation of the TLR4/MyD88/NF-κB signaling pathway in inflammation due to diabetic retinopathy[J]. Comput Math Methods Med, 2022: 3864863. doi:10.1155/2022/3864863 |
[32] | Tang L, Zhang C, Lu L, et al. Melatonin maintains inner blood-retinal barrier by regulating microglia via inhibition of PI3K/Akt/Stat3/NF-κB signaling pathways in experimental diabetic retinopathy[J]. Front Immunol, 2022, 13: 831660. doi:10.3389/fimmu.2022.831660 |
[33] | Jo DH, Yun JH, Cho CS, et al. Interaction between microglia and retinal pigment epithelial cells determines the integrity of outer blood-retinal barrier in diabetic retinopathy[J]. Glia, 2019, 67(2): 321-331. doi:10.1002/glia.23542 |
[34] | Yun JH, Park SW, Kim KJ, et al. Endothelial STAT3 activation increases vascular leakage through downregulating tight junction proteins: implications for diabetic retinopathy[J]. J Cell Physiol,2017, 232(5): 1123-1134. doi:10.1002/jcp.25575 |
[35] | Arrigo A, Aragona E, Bandello F. VEGF-targeting drugs for the treatment of retinal neovascularization in diabetic retinopathy[J]. Ann Med, 2022, 54(1): 1089-1111. doi:10.1080/07853890.2022.2064541 |
[36] | Friedman M, Azrad-lebovitz T, Morzaev D, et al. Protective effect of TLR4 ablation against corneal neovascularization following chemical burn in a mouse model[J]. Curr Eye Res,2019, 44(5): 505-513. doi:10.1080/02713683.2018.1564833 |
[37] | Chen W, Zhang J, Zhang P, et al. Role of TLR4-MAP4K4 signaling pathway in models of oxygen-induced retinopathy[J]. FASEB J, 2019, 33(3): 3451-3464. doi:10.1096/fj.201801086RR |
[38] | Gao T, Lin Z, Jin X. Hydrocortisone suppression of the expression of VEGF may relate to toll-like receptor(TLR)2 and 4[J]. Curr Eye Res, 2009, 34(9): 777-784. doi:10.1080/02713680903067919 |
[39] | Xue L, Hu M, Zhu Q, et al. GRg1 inhibits the TLR4/NF-kB signaling pathway by upregulating miR-216a-5p to reduce growth factors and inflammatory cytokines in DR[J]. Mol Biol Rep, 2023, 50(11): 9379-9394. doi:10.1007/s11033-023-08895-3 |
[40] | Kinuthia UM, Wolf A, Langmann T. Microglia and inflammatory responses in diabetic retinopathy[J]. Front Immunol, 2020,11: 564077. doi:10.3389/fimmu.2020.564077 |
[41] | Boeck M, Thien A, Wolf J, et al. Temporospatial distribution and transcriptional profile of retinal microglia in the oxygen-induced retinopathy mouse model[J]. Glia, 2020, 68(9): 1859-1873. doi:10.1002/glia.23810 |
[42] | Soni D, Sagar P, Takkar B. Diabetic retinal neurodegeneration as a form of diabetic retinopathy[J]. Int Ophthalmol, 2021,41(9):3223-3248. doi:10.1007/s10792-021-01864-4 |
[43] | Bikbova G, Oshitari T, Bikbov M. Diabetic neuropathy of the retina and inflammation: perspectives[J]. Int J Mol Sci, 2023, 24(11): 9166. doi:10.3390/ijms24119166 |
[44] | Seidel A, Liu L, Jiang YD, et al. Loss of TLR4 in endothelial cells but not Müller cells protects the diabetic retina[J]. Exp Eye Res, 2021, 206: 108557. doi:10.1016/j.exer.2021.108557 |
[45] | Park HY, Kim JH, Park CK. Neuronal cell death in the inner retina and the influence of vascular endothelial growth factor inhibition in a diabetic rat model[J]. Am J Pathol, 2014, 184(6): 1752-1762. doi:10.1016/j.ajpath.2014.02.016 |
[46] | Ferreira de Melo IM, Martins Ferreira CG, Lima da Silva Souza EH, et al. Melatonin regulates the expression of inflammatory cytokines, VEGF and apoptosis in diabetic retinopathy in rats[J]. Chem Biol Interact, 2020, 327: 109183. doi:10.1016/j.cbi.2020.109183 |
[47] | Araszkiewicz A, Zozulinska-Ziolkiewicz D. Retinal neurodegeneration in the course of diabetes-pathogenesis and clinical perspective[J]. Curr Neuropharmacol, 2016, 14(8): 805-809. doi:10.2174/1570159x14666160225154536 |
[48] | Pereiro X, Ruzafa N, Acera A, et al. Dexamethasone protects retinal ganglion cells but not Müller glia against hyperglycemia in vitro[J]. PLoS One, 2018, 13(11): e0207913. doi:10.1371/journal.pone.0207913 |
[49] | Zhao M, Li CH, Liu YL. Toll-like receptor(TLR)-2/4 expression in retinal ganglion cells in a high-glucose environment and its implications[J]. Genet Mol Res, 2016, 15(2): 10. doi:10.4238/gmr.15026998 |
[50] | Nakano Y, Shimazawa M, Ojino K, et al. Toll-like receptor 4 inhibitor protects against retinal ganglion cell damage induced by optic nerve crush in mice[J]. J Pharmacol Sci. 2017, 133(3): 176-183. doi:10.1016/j.jphs.2017.02.012 |
[51] | Liu L, Jiang YD, Steinle J. Epac1 regulates TLR4 signaling in the diabetic retinal vasculature[J]. Cytokine, 2021, 144: 155576. doi:10.1016/j.cyto.2021.155576 |
[1] | 何静,雷春燕,张美霞. 糖化血红蛋白变异指数与糖尿病视网膜病变严重程度的相关性研究[J]. 山东大学耳鼻喉眼学报, 2024, 38(2): 34-40. |
[2] | 晏慧娟,肖旭平,钟宇. IL-29和TLR4在嗜酸性粒细胞浸润鼻息肉中的表达及临床意义[J]. 山东大学耳鼻喉眼学报, 2024, 38(2): 122-127. |
[3] | 陈坤,陆慧,李磊,张帆,杨军,黄琦. 累及儿童多部位的浆细胞型Castleman病1例并文献复习[J]. 山东大学耳鼻喉眼学报, 2024, 38(1): 54-58. |
[4] | 朱晗,刘雪霞,张华. 自噬在变应性鼻炎发病的作用机制研究[J]. 山东大学耳鼻喉眼学报, 2024, 38(1): 79-86. |
[5] | 袁钰淇,曹子讷,牛晓欣,谢雨杉,苏永龙,朱思敏,张一彤,刘海琴,任晓勇,施叶雯. 外周血炎症指标在阻塞性睡眠呼吸暂停低通气综合征伴高血压中的临床意义[J]. 山东大学耳鼻喉眼学报, 2023, 37(6): 85-92. |
[6] | 袁晨阳,冯晨,王岩,李延忠,房振胜. 儿童阻塞性睡眠呼吸暂停相关血液学指标的临床研究[J]. 山东大学耳鼻喉眼学报, 2023, 37(6): 145-152. |
[7] | 崔宁,王云梦,杨景朴. 2型固有淋巴细胞在慢性鼻窦炎中的作用及调节机制研究进展[J]. 山东大学耳鼻喉眼学报, 2023, 37(4): 153-159. |
[8] | 周加敏,宋玉婉,孙岩. 细胞焦亡在老年退行性疾病中的研究进展[J]. 山东大学耳鼻喉眼学报, 2023, 37(4): 172-180. |
[9] | 王惟一,时蕾,张志玉,张贵玲,时光刚. 高脂饮食对过敏性鼻炎小鼠致敏影响和肠道菌群改变的研究[J]. 山东大学耳鼻喉眼学报, 2023, 37(3): 21-29. |
[10] | 唐慧新,李景景,邹红. 阈值下微脉冲激光光凝作用机制及临床应用[J]. 山东大学耳鼻喉眼学报, 2023, 37(3): 143-148. |
[11] | 李聪,李玲,刘亭彦, 陈良. 氨基糖苷类抗生素耳毒性影响因素研究进展[J]. 山东大学耳鼻喉眼学报, 2023, 37(2): 128-134. |
[12] | 李孟婷,何书喜,王华. 炎症因子在圆锥角膜中的研究进展[J]. 山东大学耳鼻喉眼学报, 2023, 37(2): 151-158. |
[13] | 刘通,林玮,冯萌,杨依,刘婷婷,张敏. 基于网络药理学分析小檗碱在免疫微环境中对糖尿病视网膜病变的作用及实验验证[J]. 山东大学耳鼻喉眼学报, 2023, 37(1): 94-104. |
[14] | 朱晶,张睿,赵媛,李炀,樊孟耘,赵昱. 内镜下低温等离子消融治疗不同炎症分期先天性梨状窝瘘45例[J]. 山东大学耳鼻喉眼学报, 2022, 36(5): 24-29. |
[15] | 王娇娇,李苗宋宗明. 糖尿病视网膜病变的机制和细胞模型研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(5): 93-99. |
|