[1]黄玉婷,李晓洁,郑香悦,等.湿性年龄相关性黄斑变性患者抗血管内皮生长因子治疗敏感性的影响因素：基于房水细胞因子分析[J].眼科新进展,2021,41(3):240-243.[doi:10.13389/j.cnki.rao.2021.0050]
　HUANG Yuting,LI Xiaojie,ZHENG Xiangyue,et al.Analysis of factors influencing the sensitivity of anti vascular endothelial growth factor therapy in patients with wet age-related macular degeneration based on aqueous humor cytokines[J].Recent Advances in Ophthalmology,2021,41(3):240-243.[doi:10.13389/j.cnki.rao.2021.0050]
点击复制

湿性年龄相关性黄斑变性患者抗血管内皮生长因子治疗敏感性的影响因素：基于房水细胞因子分析/HTML
分享到：

《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
41卷
期数:
2021年3期
页码:
240-243
栏目:
应用研究
出版日期:
2021-03-05

文章信息/Info

Title:
Analysis of factors influencing the sensitivity of anti vascular endothelial growth factor therapy in patients with wet age-related macular degeneration based on aqueous humor cytokines
作者:
黄玉婷; 李晓洁; 郑香悦; 俞晓艺; 关国华
510405　广东省广州市，广州中医药大学第一附属医院
Author(s):
HUANG Yuting; LI Xiaojie; ZHENG Xiangyue; YU Xiaoyi; GUAN Guohua
The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine,Guangzhou 510405,Guangdong Province,China
关键词:
湿性年龄相关性黄斑变性; 抗VEGF治疗; 房水细胞因子; 敏感性
Keywords:
wet age-related macular degeneration;  anti-VEGF treatment;  cytokines in aqueous humor;  sensibility
分类号:
R774.5
DOI:
10.13389/j.cnki.rao.2021.0050
文献标志码:
A
摘要:
目的　通过分析湿性年龄相关性黄斑变性（wAMD）患者抗血管内皮生长因子（VEGF）治疗后房水细胞因子浓度的改变及房水细胞因子与相关指标之间的相关性，探讨影响wAMD患者抗VEGF治疗敏感性的因素。方法　选取2019年8月至2020年1月于广州中医药大学第一附属医院就诊的wAMD患者（观察组）和白内障患者（对照组）各30例（30眼），分别收集两组患者研究期间房水，用微球悬浮阵列技术（Luminex200TM）进行房水细胞因子浓度检测。同时分析观察组患者连续2次抗VEGF（雷珠单抗或康柏西普）治疗前后相关指标［最佳矫正视力、黄斑中心凹视网膜厚度（CMT)］与房水细胞因子之间的相关性。结果　抗VEGF治疗前，观察组患者房水中白细胞介素-8（IL-8）、血管生成素样蛋白4（angiopoietin-like protein 4，ANGPTL4）、单核细胞趋化蛋白-1（MCP-1）浓度均明显高于对照组，差异均有统计学意义（均为P＜0.05）；而两组患者房水中血管内皮生长因子-A（VEGF-A）、白细胞介素-6（IL-6）、血小板源性生长因子-BB（PDGF-BB）细胞因子浓度差异均无统计学意义（均为P＞0.05）；抗VEGF治疗1个月后，观察组患者房水中VEGF-A浓度明显下降，与治疗前相比差异具有统计学意义（Z=-3.589，P＜0.001）；连续2个月抗VEGF治疗后，观察组患者视力提高，CMT降低，差异均有统计学意义（均为P＜0.05）；抗VEGF治疗前后观察组患者房水中PDGF-BB浓度与视力呈负相关（r=-0.413、-0.508，均为P＜0.05）,治疗1个月后MCP-1、IL-6、ANGPTL4浓度与CMT均呈正相关（r=0.743、0.552、0.566，均为P＜0.05）。结论　房水细胞因子IL-8、MCP-1、ANGPTL4可能参与wAMD疾病的发生，抗VEGF治疗能有效改善患者视力及减轻黄斑水肿，其中视力恶化可能与房水细胞因子PDGF-BB浓度有关，而房水细胞因子MCP-1、IL-6、ANGPTL4浓度可能与黄斑水肿有关。
Abstract:
Objective　To analyze the changes of cytokines in aqueous humor of patients with wet age-related macular degeneration (wAMD) after anti vascular endothelial growth factor (VEGF) treatment and the correlation between cytokines in aqueous humor and related therapeutic indexes, and the factors affecting the sensitivity of anti-VEGF treatment in wAMD patients were discussed.Methods　From August 2019 to January 2020, 30 patients (30 eyes) with wAMD and 30 patients (30 eyes) with cataract in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine were selected as the observation group and the control group, respectively. The aqueous humor of the two groups was collected during the study period, and the concentrations of cytokines in aqueous humor were detected by (microsphere) suspension array technology (Luminex 200). At the same time, the correlation between the related indexes ［best corrected visual acuity(BCVA),macular fovea thickness (CMT)］ and the cytokines in the aqueous humor before and after two consecutive anti-VEGF (ranibizumab or conbercept) treatment in the observation group was analyzed.Results　Before anti-VEGF treatment, the concentrations of interleukin-8 (IL-8), angiopoietin-like protein 4 (ANGPTL4) and monocyte chemotactic protein-1 (MCP-1) in aqueous chamber in observation group were significantly higher than those in control group, with statistical significance (all P<0.05), while the concentrations of vascular endothelial growth factor-A (VEGF-A), interleukin-6 (IL-6), IL-8,and platelet-derived growth factor-BB (PDGF-BB) in the aqueous humor of the two groups were not significantly different (all P>0.05). After 1 month of anti-VEGF treatment, the concentration of VEGF-A in aqueous humor of the observation group decreased significantly, the difference was statistically significant (Z=-3.589,P<0.001). After 2 months of anti-VEGF treatment, the visual acuity of the observation group was improved, and CMT was decreased, with statistical significance (all P<0.05). Before anti-VEGF treatment, the concentrations of PDGF-BB cytokines in aqueous humor of the observation group were negatively correlated with the visual acuity (r=-0.413, -0.508, both P<0.05), and the concentrations of MCP-1, IL-6, and ANGPTL4 cytokines were positively correlated with CMT after 1 month of treatment (r=0.743, 0.552, 0.566, all P<0.05).Conclusion　Aqueous humor cytokines IL-8, MCP-1 and ANGPTL4 may be involved in the occurrence of wAMD. Anti-VEGF can effectively improve the vision of patients and reduce macular edema. The deterioration of vision may be related to PDGF-BB, while MCP-1, IL-6 and ANGPTL4 may be related to macular edema.

参考文献/References:

［1］　WONG W L,SU X Y,LI X,CHEUNG C M,KLEIN R,CHENG C Y,et al.Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040:a systematic review and meta-analysis［J］.Lancet Glob Health，2014,2(2):106-116.
［2］　许凯,梁丽娜.干性年龄相关性黄斑变性的治疗研究进展［J］.中国实用眼科杂志,2016,34(11):1134-1136.
XU K,LIANG L N.Advances in the treatment of dry age-related macular degeneration ［J］.Chin J Pract Ophthalmol,2016,34(11):1134-1136.
［3］　全国眼底病研究协作小组：老年性黄斑变性临床诊断标准［J］.眼科新进展，1986,6(4):14-15.
National Fundus Disease Research Cooperation Group.Clinical diagnostic criteria for age-related macular degeneration［J］.Rec Adv Ophthalmol,1986,6(4):14-15.
［4］　EGHOJ M S,SORENSEN T L.Tachyphylaxis during treatment of exudative age-related macular degeneration with ranibizumab［J］.Br J Ophthalmol,2012,96(1):21-23.
［5］　程子芳,王海燕,王雨生.抗血管内皮生长因子药物治疗新生血管性老年性黄斑变性应答不良及无应答现象机制研究的进展［J］.中华眼底病杂志,2017,33(2):199-202.
CHENG Z F,WANG H Y,WANG Y S.Advances in the mechanism of poor response and non-response in the treatment of neovascular amd with anti-vascular endothelial growth factor drugs［J］.Chin J Ocul Fundus Dis,2017,33(2):199-202.
［6］　JONA S J B,TAO Y,NEUMAIER M,FINDEISEN P.Cytokine concentration in aqueous humour of eyes with exudative age-related macular degeneration［J］.Acta Ophthalmol,2012,90(5):381-388.
［7］　KNICKELBEIN J E,CHAN C C,SEN H N,FERRIS F L, NUSSENBLATT R B.Inflammatory mechanisms of age-related macular degeneration［J］.Int Ophthalmol Clin,2015,55(3)：63-78.
［8］　VESSEY K A,WAUGH M,JOBLING A I,PHIPPS J A,HO T,TROGRLIC L,et al.Assessment of retinal function and morphology in aging ccl2 knockout mice［J］.Invest Ophthalmol Vis Sci,2015,56(2):1238-1252.
［9］　KLUEH U,CZAJKOWSKI C,LUDZINSK I,QIAO Y,FRAILE J,KREUTZER D.Impact of ccl2 and ccr2 chemokine/receptor deficiencies on macrophage recruitment and continuous glucose monitoring in vivo［J］.Biosensors Bioelectr,2016,86(default):262-269.
［10］　JONAS J B,TAO Y,NEUMAIER M,FINDEISEN P.Monocyte chemoattractant protein 1,intercellular adhesion molecule 1,and vascular cell adhesion molecule 1 in exudative age-related macular degeneration［J］.Arch Ophthalmol,2010,128(10):1281-1286.
［11］　宋钊,庞婷婷,范右飞，王玉林.IL-8与肺动脉高压大鼠血管重构和血管新生的关系［J］.新医学,2013,44(7):76-80.
SONG Z,PANG T T,FAN Y F,WANG Y L.The relationship between IL-8 and vascular remodeling and angiogenesis in pulmonary hypertension rats［J］.New Med,2013,44(7):76-80.
［12］　林菁,包欣,谢田华,姚勇.增生性糖尿病视网膜病变患者房水及玻璃体中IL-8、CXCR1、CXCR2表达及意义［J］.临床眼科杂志,2019,27(2):101-105.
LIN J,BAO X,XIE T H,YAO Y.Expression and significance of IL-8,CXCR1 and CXCR2 in the aqueous fluid and vitreous of patients with proliferative diabetic retinopathy［J］.J Clin Ophthalmol,2019,27(2):101-105.
［13］　GROOTAERT C,van De WIELE T,VERSTRAETE W,BRACKE M,VANHOECKE B.Angiopoietin-like protein 4:health effects,modulating agents and structure-function relationships［J］.Expert Rev Proteomics,2012,9(2):181-199.
［14］　YANG X Y,CHENG Y,SU G F.A review of the multifunctionality of angiopoietin-like 4 in eye disease［J］.Biosci Rep,2018，38（5）:BSR20180557.
［15］　FAUSER S,VIEBAHN U,MUETHER P S.Intraocular and systemic inflammation-related cytokines during one year of ranibizumab treatment for neovascular age-related macular degeneration［J］.Acta Ophthalmol,2015,93(8):734-738.
［16］　AGAWA T,USUI Y,WAKABAYASHI Y,OKUNUKI Y,JUAN M.Profile of intraocular immune mediators in patients with age-related macular degeneration and the effect of intravitreal bevacizumab injection［J］.Retina,2014,34(9):1811-1818.
［17］　REZAR-DREINDL S,SACU S,EIBENBERGER K,POLLREISZ A,BUHL W.The intraocular cytokine profile and therapeutic response in persistent neovascular age-related macular degeneration［J］.Invest Ophthalmol Vis Sci,2016,57(10):4144-4150.
［18］　YOKOUCHI H,ETO K,NISHIMURA W,TAKEDA N,KABURAGI Y,YAMAMOTO S,et al.Angiopoietin-like protein 4 (ANGPTL4) is induced by high glucose in retinal pigment epithelial cells and exhibits potent angiogenic activity on retinal endothelial cells［J］.Acta Ophthalmol,2013,91(4):289-297.
［19］　BABAPOOR-FARROKHRAN S,JEE K,PUCHNE B,HASSAN S J,XIN X B,RODRIGUES M,et al,Angiopoietin-like 4 is a potent angiogenic factor and a novel therapeutic target for patients with proliferative diabetic retinopathy［J］.Proc Natl Acad USA,2015,112(23)：3030-3039.
［20］　SIEDLECKI J,WERTHEIMER C,WOLF A,LIEGL R,PRIGLINGER C,PRIGLINGER S,et al.Combined VEGF and PDGF inhibition for neovascular AMD:anti-angiogenic properties of axitinib on human endothelial cells and pericytes in vitro［J］.Graefes Arch Clin Exp Ophthalmol,2017,255(5):963-972.
［21］　谷潇雅.细胞因子在渗出性年龄相关性黄斑变性中的表达及靶向治疗［J］.中华实验眼科杂志,2015,33(1):93-96.
GU X Y.Expression of cytokines in exudative age-related macular degeneration and targeted therapy ［J］.Chin J Exp Ophthalmol,2015,33(1):93-96.
［22］　DING K,EATON L,BOWLEY D,RIESER M,CHANG Q,HARRIS M C,et al.Generation and characterization of ABBV642,a dual variable domain immunoglobulin molecule (DVD-Ig) that potently neutralizes VEGF and PDGF-BB and is designed for the treatment of exudative age-related macular degeneration［J］.Mabs,2017,9(2):269-284.

相似文献/References:

[1]施晨蕾 王亚冬.湿性年龄相关性黄斑变性患者光感受器细胞层变化与视力的相关性研究[J].眼科新进展,2013,33(11):000.
[2]肖昂,周琼.Aflibercept治疗湿性AMD和黄斑水肿的相关研究现状[J].眼科新进展,2014,34(6):598.[doi:10.13389/j.cnki.rao.2014.0165]
[3]蒋胜群,高自清,王剑锋,等.外周血淋巴细胞DNA损伤与湿性年龄相关性黄斑变性的关系[J].眼科新进展,2018,38(8):769.[doi:10.13389/j.cnki.rao.2018.0181]
　JIANG Sheng-Qun,GAO Zi-Qing,WANG Jian-Feng,et al.Relationship between the DNA damage of peripheral blood lymphocyte and wet age-related macular degeneration[J].Recent Advances in Ophthalmology,2018,38(3):769.[doi:10.13389/j.cnki.rao.2018.0181]
[4]付燕,张月玲,王丽英,等.湿性年龄相关性黄斑变性患者抗VEGF治疗无效的因素分析和视功能预后[J].眼科新进展,2021,41(3):254.[doi:10.13389/j.cnki.rao.2021.0053]
　FU Yan,ZHANG Yueling,WANG Liying,et al.Factors and outcomes associated with failure to anti-VEGF treatment in patients with wet age-related macular degeneration[J].Recent Advances in Ophthalmology,2021,41(3):254.[doi:10.13389/j.cnki.rao.2021.0053]
[5]张敬法,赵珍珍.湿性年龄相关性黄斑变性发病机制及治疗[J].眼科新进展,2022,42(2):085.[doi:10.13389/j.cnki.rao.2022.0019]
　ZHANG Jingfa,ZHAO Zhenzhen.Pathogenesis and treatment of wet age-related macular degeneration[J].Recent Advances in Ophthalmology,2022,42(3):085.[doi:10.13389/j.cnki.rao.2022.0019]
[6]姚盼盼,范亮亮,张洁,等.抗VEGF治疗对不同类型DME患者黄斑中心凹无血管区的影响[J].眼科新进展,2023,43(1):030.[doi:10.13389/j.cnki.rao.2023.0006]
　YAO Panpan,FAN Liangliang,ZHANG Jie,et al.Effect of anti-vascular endothelial growth factor therapy on the foveal avascular zone in patients with different types of diabetic macular edema[J].Recent Advances in Ophthalmology,2023,43(3):030.[doi:10.13389/j.cnki.rao.2023.0006]
[7]肇莉莉,王萍,孙连义,等.HTRA3基因对脉络膜新生血管和M2型巨噬细胞极化的影响[J].眼科新进展,2024,44(4):275.[doi:10.13389/j.cnki.rao.2024.0054]
　ZHAO Lili,WANG Ping,SUN Lianyi,et al.Effect of HtrA serine peptidase 3 gene on choroidal neovascularization and M2 macrophage polarization[J].Recent Advances in Ophthalmology,2024,44(3):275.[doi:10.13389/j.cnki.rao.2024.0054]

备注/Memo

备注/Memo:
国家中医药管理局项目（编号：2019XZZX-YK003）；关国华全国名老中医药专家传承工作室［编号：国中医药人教函（2018）134号］；广州中医药大学2019年学科研究重大项目（编号：XK2019015）
更新日期/Last Update: 2021-03-05