Research progress on the roles of aqueous humor inflammatory factors in the pathogenesis of diabetic macular edema

doi:10.3760/cma.j.issn.1007-1245.2023.17.001

Abstract

Abstract:

Diabetic retinopathy (DR) is an important cause of vision loss in diabetic patients. Globally, 6.8% of diabetics aged 20 to 79 years develop diabetic macular edema (DME). Studies have found that DME is mediated by inflammatory factors and vascular endothelial growth factor (VEGF), and the effects of the two are correlated. Inflammation plays an important role in the pathogenesis of DME, involving a variety of chemokines and cytokines. The levels of inflammatory factors in aqueous humor are closely related to the severity of DME. This article reviews the roles of inflammatory factors in aqueous humor in the pathogenesis of DME.

Key words:

Diabetic macular edema, Tumor necrosis factor-α, Interleukin, Interferon inducible protein-10, Monocyte chemotactic protein, , Integrin, Progress

摘要：

糖尿病性视网膜病变（DR）是导致糖尿病患者视力下降的重要原因。在全球范围内，20～79岁的糖尿病患者中，有6.8%的患者可出现糖尿病性黄斑水肿（DME）。DME是由炎症因子和血管内皮生长因子（VEGF）介导的，两者的作用是相互关联的。炎症在DME的发病机制中起着至关重要的作用，涉及多种趋化因子和细胞因子。房水中炎性因子的水平与DME的严重程度密切相关。本文就房水中炎性因子在DME发病机制中的作用进行综述。

关键词:

糖尿病性黄斑水肿, , , 肿瘤坏死因子-α, , , 白细胞介素, 干扰素诱导蛋白-10, 单核细胞趋化蛋白, 整合素, 进展

Niu Huan, Cong Chenyang.

Research progress on the roles of aqueous humor inflammatory factors in the pathogenesis of diabetic macular edema [J]. International Medicine and Health Guidance News, 2023, 29(17): 2369-2372.

牛欢丛晨阳.

房水炎性因子在糖尿病性黄斑水肿发病机制中的研究进展 [J]. 国际医药卫生导报, 2023, 29(17): 2369-2372.

References

[1] Holekamp NM. Overview of diabetic macular edema[J]. Am J Manag Care, 2016, 22(10 Suppl):s284-s291.
[2] Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy[J]. Diabetes Care, 2012, 35(3):556-564. DOI: 10.2337/dc11-1909.
[3] Antonetti DA, Lieth E, Barber AJ, et al. Molecular mechanisms of vascular permeability in diabetic retinopathy[J]. Semin Ophthalmol, 1999, 14(4):240-248. DOI: 10.3109/08820539909069543.
[4] Writing Committee for the Diabetic Retinopathy Clinical Research Network; Gross JG, Glassman AR, et al. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial[J]. JAMA, 2015, 314(20):2137-2146. DOI: 10.1001/jama.2015.15217.
[5] Tan GS, Cheung N, Simó R, et al. Diabetic macular oedema[J]. Lancet Diabetes Endocrinol, 2017, 5(2):143-155. DOI: 10.1016/S2213-8587(16)30052-3.
[6] Udaondo P, Hernández C, Briansó-Llort L, et al. Usefulness of liquid biopsy biomarkers from aqueous humor in predicting anti-VEGF response in diabetic macular edema: results of a pilot study[J]. J Clin Med, 2019, 8(11):1841. DOI: 10.3390/jcm8111841.
[7] Capitão M, Soares R. Angiogenesis and inflammation crosstalk in diabetic retinopathy[J]. J Cell Biochem, 2016, 117(11):2443-2453. DOI: 10.1002/jcb.25575.
[8] Behl Y, Krothapalli P, Desta T, et al. Diabetes-enhanced tumor necrosis factor-alpha production promotes apoptosis and the loss of retinal microvascular cells in type 1 and type 2 models of diabetic retinopathy[J]. Am J Pathol, 2008, 172(5):1411-1418. DOI: 10.2353/ajpath. 2008.071070.
[9] Hassan I, Luo Q, Majumdar S, et al. Tumor necrosis factor alpha (TNF-α) disrupts Kir4.1 channel expression resulting in Müller cell dysfunction in the retina[J]. Invest Ophthalmol Vis Sci, 2017, 58(5):2473-2482. DOI: 10.1167/iovs.16-20712.
[10] Yao Y, Li R, Du J, et al. Tumor necrosis factor-α and diabetic retinopathy: review and meta-analysis[J]. Clin Chim Acta, 2018, 485:210-217. DOI: 10.1016/j.cca.2018. 06.028.
[11] Xu J, Liao YF, Zhou WP, et al. The MCP-1 gene A-2518G polymorphism confers an increased risk of vascular complications in type 2 diabetes mellitus patients[J]. Genet Test Mol Biomarkers, 2015, 19(8):411-417. DOI: 10.1089/gtmb.2014.0325.
[12] Deshmane SL, Kremlev S, Amini S, et al. Monocyte chemoattractant protein-1 (MCP-1): an overview[J]. J Interferon Cytokine Res, 2009, 29(6):313-326. DOI: 10.1089/jir.2008.0027.
[13] Forbes JM, Cooper ME. Mechanisms of diabetic complications[J]. Physiol Rev, 2013, 93(1):137-188. DOI: 10.1152/physrev.00045.2011.
[14] Jiang Z, Hennein L, Xu Y, et al. Elevated serum monocyte chemoattractant protein-1 levels and its genetic polymorphism is associated with diabetic retinopathy in Chinese patients with type 2 diabetes[J]. Diabet Med, 2016, 33(1):84-90. DOI: 10.1111/dme.12804.
[15] Kaštelan S, Orešković I, Bišćan F, et al. Inflammatory and angiogenic biomarkers in diabetic retinopathy[J]. Biochem Med (Zagreb), 2020, 30(3):030502. DOI: 10.11613/BM.2020.030502.
[16] Adki KM, Kulkarni YA. Potential biomarkers in diabetic retinopathy[J]. Curr Diabetes Rev, 2020, 16(9):971-983. DOI: 10.2174/1573399816666200217092022.
[17] Khuu LA, Tayyari F, Sivak JM, et al. Aqueous humour concentrations of TGF-β, PLGF and FGF-1 and total retinal blood flow in patients with early non-proliferative diabetic retinopathy[J]. Acta Ophthalmol, 2017, 95(3):e206-e211. DOI: 10.1111/aos.13230.
[18] Kishimoto T. The biology of interleukin-6[J]. Blood, 1989, 74(1):1-10.
[19] 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.
[20] Zahir-Jouzdani F, Atyabi F, Mojtabavi N. Interleukin-6 participation in pathology of ocular diseases[J]. Pathophysiology, 2017, 24(3):123-131. DOI: 10.1016/j.pathophys.2017.05.005.
[21] Valle ML, Dworshak J, Sharma A, et al. Inhibition of interleukin-6 trans-signaling prevents inflammation and endothelial barrier disruption in retinal endothelial cells[J]. Exp Eye Res, 2019, 178:27-36. DOI: 10.1016/j.exer.2018.09.009.
[22] Daruich A, Matet A, Moulin A, et al. Mechanisms of macular edema: Beyond the surface[J]. Prog Retin Eye Res, 2018, 63:20-68. DOI: 10.1016/j.preteyeres.2017. 10.006.
[23] Ye EA, Steinle JJ. miR-146a suppresses STAT3/VEGF pathways and reduces apoptosis through IL-6 signaling in primary human retinal microvascular endothelial cells in high glucose conditions[J]. Vision Res, 2017, 139:15-22. DOI: 10.1016/j.visres.2017.03.009.
[24] Chalam KV, Grover S, Sambhav K, et al. Aqueous interleukin-6 levels are superior to vascular endothelial growth factor in predicting therapeutic response to bevacizumab in age-related macular degeneration[J]. J Ophthalmol, 2014, 2014:502174. DOI: 10.1155/2014/502174.
[25] Xie K. Interleukin-8 and human cancer biology[J]. Cytokine Growth Factor Rev, 2001, 12(4):375-391. DOI: 10.1016/s1359-6101(01)00016-8.
[26] Jonas JB, Jonas RA, Neumaier M, et al. Cytokine concentration in aqueous humor of eyes with diabetic macular edema[J]. Retina, 2012, 32(10):2150-2157. DOI: 10.1097/IAE.0b013e3182576d07.
[27] Lee WJ, Kang MH, Seong M, et al. Comparison of aqueous concentrations of angiogenic and inflammatory cytokines in diabetic macular oedema and macular oedema due to branch retinal vein occlusion[J]. Br J Ophthalmol, 2012, 96(11):1426-1430. DOI: 10.1136/bjophthalmol-2012- 301913.
[28] Kwon JW, Jee D. Aqueous humor cytokine levels in patients with diabetic macular edema refractory to anti-VEGF treatment[J]. PLoS One, 2018, 13(9):e0203408. DOI: 10.1371/journal.pone.0203408.
[29] Dinarello CA, van der Meer JW. Treating inflammation by blocking interleukin-1 in humans[J]. Semin Immunol, 2013, 25(6):469-484. DOI: 10.1016/j.smim.2013.10.008.
[30] Carmi Y, Dotan S, Rider P, et al. The role of IL-1β in the early tumor cell-induced angiogenic response[J]. J Immunol, 2013, 190(7):3500-3509. DOI: 10.4049/jimmunol.1202769.
[31] Lim SW, Bandala-Sanchez E, Kolic M, et al. The influence of intravitreal ranibizumab on inflammation-associated cytokine concentrations in eyes with diabetic macular edema[J]. Invest Ophthalmol Vis Sci, 2018, 59(13):5382-5390. DOI: 10.1167/iovs.17-23325.
[32] Kowluru RA, Odenbach S. Role of interleukin-1beta in the pathogenesis of diabetic retinopathy[J]. Br J Ophthalmol, 2004, 88(10):1343-1347. DOI: 10.1136/bjo.2003.038133.
[33] Loetscher M, Gerber B, Loetscher P, et al. Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes[J]. J Exp Med, 1996, 184(3):963-969. DOI: 10.1084/jem.184.3.963.
[34] Dong L, Bai J, Jiang X, et al. The gene polymorphisms of IL-8(-251T/A) and IP-10(-1596C/T) are associated with susceptibility and progression of type 2 diabetic retinopathy in northern Chinese population[J]. Eye (Lond), 2017, 31(4):601-607. DOI: 10.1038/eye.2016.287.
[35] Joy SS, Siddiqui K. Molecular and pathophysiological mechanisms of diabetic retinopathy in relation to adhesion molecules[J]. Curr Diabetes Rev, 2019, 15(5):363-371. DOI: 10.2174/1573399814666181017103844.
[36] Hu TT, Vanhove M, Porcu M, et al. The potent small molecule integrin antagonist THR-687 is a promising next-generation therapy for retinal vascular disorders[J]. Exp Eye Res, 2019, 180:43-52. DOI: 10.1016/j.exer.2018.11.022.
[37] Jawhara S, Pluskota E, Cao W, et al. Distinct effects of integrins αXβ2 and αMβ2 on leukocyte subpopulations during inflammation and antimicrobial responses[J]. Infect Immun, 2016, 85(1):e00644-16. DOI: 10.1128/IAI.00644-16.