[1]李桐栖,孔德平,孙晓东.巨噬细胞代谢重编程在新生血管性年龄相关性黄斑变性中的作用研究进展[J].眼科新进展,2023,43(11):920-924.[doi:10.13389/j.cnki.rao.2023.0184]
　LI Tongqi,KONG Deping,SUN Xiaodong.Research progress on the metabolic reprogramming of macrophages in neovascular age-related macular degeneration[J].Recent Advances in Ophthalmology,2023,43(11):920-924.[doi:10.13389/j.cnki.rao.2023.0184]
点击复制

巨噬细胞代谢重编程在新生血管性年龄相关性黄斑变性中的作用研究进展/HTML
分享到：

《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
43卷
期数:
2023年11期
页码:
920-924
栏目:
文献综述
出版日期:
2023-11-05

文章信息/Info

Title:
Research progress on the metabolic reprogramming of macrophages in neovascular age-related macular degeneration
作者:
李桐栖; 孔德平; 孙晓东
200071　上海市，上海交通大学医学院附属第一人民医院眼科（李桐栖，孙晓东)；201620　上海市，上海交通大学医学院附属第一人民医院疑难疾病精准研究中心(孔德平)
Author(s):
LI Tongqi1; KONG Deping2; SUN Xiaodong1
1.Department of Ophthalmology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200071,China
2.Precision Research Center for Refractory Diseases,Institute for Clinical Research,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 201620,China
关键词:
巨噬细胞; 代谢重编程; 脉络膜新生血管
Keywords:
macrophage;  metabolic reprogramming;  choroidal neovascularization
分类号:
R774.5
DOI:
10.13389/j.cnki.rao.2023.0184
文献标志码:
A
摘要:
巨噬细胞是调节组织稳态与修复重塑的关键免疫细胞。在新生血管性年龄相关性黄斑变性（NVAMD）的发展过程中，巨噬细胞对调节脉络膜新生血管至关重要。由于其高可塑性和功能异质性，尚不明确巨噬细胞的调节机制。新近研究发现，代谢重编程是巨噬细胞效应功能调节的关键因素。在脉络膜新生血管的发生发展过程中，巨噬细胞受到微环境刺激及全身因素调节，其代谢途径重新编程，从而显著改变功能表型，影响NVAMD的发生发展。因此，深入了解巨噬细胞促血管新生表型的代谢变化及形成机制，有望为NVAMD治疗提供新靶点。
Abstract:
Macrophages are key immune cells that regulate homeostasis, repair and remodeling of tissues. In the development of neovascular age-related macular degeneration (NVAMD), macrophages are essential for regulating choroidal neovascularization (CNV). Macrophages are characterized by high plasticity and functional heterogeneity, and their regulatory mechanism has not been clear. New studies have revealed that metabolic reprogramming is a key factor in regulating the effect and function of macrophages. During the occurrence and development of CNV, macrophages are regulated by microenvironment stimuli and systemic factors, and their metabolic pathways are reprogrammed and significantly alter the phenotype and function, which subsequently affect the occurrence and development of NVAMD. Therefore, an in-depth understanding of the metabolic changes and mechanisms underlying the pro-angiogenic phenotype of macrophages is expected to provide new targets for the treatment of NVAMD.

参考文献/References:

［1］　SPAIDE R F,JAFFE G J,SARRAF D,FREUND K B,SADDA S R,STAURENGHI G，et al.Consensus nomenclature for reporting neovascular age-related macular degeneration data:consensus on neovascular age-related macular degeneration nomenclature study group［J］.Ophthalmology,2020,127(5):616-636.
［2］　CATT Research Group;MARTIN D F,MAGUIRE M G,YING G S,GRUNWALD J E,FINE S L,et al.Ranibizumab and bevacizumab for neovascular age-related macular degeneration［J］.N Engl J Med,2011,364(20):1897-1908.
［3］　HEIER J S,BROWN D M,CHONG V,KOROBELNIK J F,KAISER P K,NGUYEN Q D，et al.Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration［J］.Ophthalmology,2012,119(12):2537-2548.
［4］　罗曼，陈晓隆.新生血管性年龄相关性黄斑变性患者玻璃体内注射抗血管内皮生长因子药物治疗进展［J］.眼科新进展,2020,40(6):582-586.
LUO M,CHEN X L.Progress in treatment of neovascular age-related macular degeneration with intravitreal injection of anti-VEGF drugs［J］.Rec Adv Ophthalmol,2020,40(6):582-586.
［5］　DELPRAT VMICHIELS C.A bi-directional dialog between vascular cells and monocytes/macrophages regulates tumor progression［J］.Cancer Metastasis Rev,2021,40(2):477-500.
［6］　ZHU C,KROS J M,CHENG CMUSTAFA D.The contribution of tumor-associated macrophages in glioma neo-angiogenesis and implications for anti-angiogenic strategies［J］.Neuro Oncol,2017,19(11):1435-1446.
［7］　MCLEOD D S,BHUTTO I,EDWARDS M M,SILVER R E,SEDDON J MLUTTY G A.Distribution and quantification of choroidal macrophages in human eyes with age-related macular degeneration［J］.Invest Ophthalmol Vis Sci,2016,57(14):5843-5855.
［8］　SAKURAI E,ANAND A,AMBATI B K,VAN ROOIJEN NAMBATI J.Macrophage depletion inhibits experimental choroidal neovascularization［J］.Invest Ophthalmol Vis Sci,2003,44(8):3578-3585.
［9］　TSUTSUMI C,SONODA K H,EGASHIRA K,QIAO H,HISATOMI T,NAKAO S，et al.The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization［J］.J Leukoc Biol,2003,74(1):25-32.
［10］　APTE R S,RICHTER J,HERNDON JFERGUSON T A.Macrophages inhibit neovascularization in a murine model of age-related macular degeneration［J］.PLoS Med,2006,3(8):e310.
［11］　SHAPOURI-MOGHADDAM A,MOHAMMADIAN S,VAZINI H,TAGHADOSI M,ESMAEILI S A,MARDANI F，et al.Macrophage plasticity,polarization,and function in health and disease［J］.J Cell Physiol,2018,233(9):6425-6440.
［12］　NAKAMURA R,SENE A,SANTEFORD A,GDOURA A,KUBOTA S,ZAPATA N，et al.IL10-driven STAT3 signalling in senescent macrophages promotes pathological eye angiogenesis［J］.Nat Commun,2015,6:7847.
［13］　XU Y,CUI K,LI J,TANG X,LIN J,LU X，et al.Melatonin attenuates choroidal neovascularization by regulating macrophage/microglia polarization via inhibition of RhoA/ROCK signaling pathway［J］.J Pineal Res,2020,69(1):e12660.
［14］　WILLENBORG S,SANIN D E,JAIS A,DING X,ULAS T,NCHEL J，et al.Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing［J］.Cell Metab,2021,33(12):2398-2414.
［15］　ROH M I,KIM H S,SONG J H,LIM J B,KOH H，JKWON O W.Concentration of cytokines in the aqueous humor of patients with naive,recurrent and regressed CNV associated with AMD after bevacizumab treatment［J］.Retina,2009,29(4):523-529.
［16］　WILLENBORG S,LUCAS T,VAN LOO G,KNIPPER J A,KRIEG T,HAASE I，et al.CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair［J］.Blood,2012,120(3):613-625.
［17］　LAVALETTE S,RAOUL W,HOUSSIER M,CAMELO S,LEVY O,CALIPPE B，et al.Interleukin-1β inhibition prevents choroidal neovascularization and does not exacerbate photoreceptor degeneration［J］.Am J Pathol,2011,178(5):2416-2423.
［18］　IZUMI-NAGAI K,NAGAI N,OZAWA Y,MIHARA M,OHSUGI Y,KURIHARA T，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.
［19］　VAN DEN BOSSCHE J,O’NEILL L,AMENON D.Macrophage immunometabolism:where are we (going)?［J］.Trends Immunol,2017,38(6):395-406.
［20］　O’NEILL L A J,KISHTON R,JRATHMELL J.A guide to immunometabolism for immunologists［J］.Nat Rev Immunol,2016,16(9):553-565.
［21］　PALSSON-MCDERMOTT E M,CURTIS A M,GOEL G,LAUTERBACH M A,SHEEDY F J,GLEESON L E，et al.Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-activated macrophages［J］.Cell Metab.,2015,21(1):65-80.
［22］　LUO W,HU H,CHANG R,ZHONG J,KNABEL M,O’MEALLY R，et al.Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1［J］.Cell,2011,145(5):732-744.
［23］　MOON J S,HISATA S,PARK M A,DENICOLA GINA M,RYTER STEFAN W,NAKAHIRA K，et al.mTORC1-induced HK1-dependent glycolysis regulates NLRP3 inflammasome activation［J］.Cell Rep,2015,12(1):102-115.
［24］　CHANG C H,CURTIS J D,MAGGI L B,Jr,FAUBERT B,VILLARINO A V,O’SULLIVAN D，et al.Posttranscriptional control of T cell effector function by aerobic glycolysis［J］.Cell,2013,153(6):1239-1251.
［25］　GALVN-PEA S,CARROLL R G,NEWMAN C,HINCHY E C,PALSSON-MCDERMOTT E,ROBINSON E K，et al.Malonylation of GAPDH is an inflammatory signal in macrophages［J］.Nat Commun,2019,10(1):338.
［26］　WANG J,YANG P,YU T,GAO M,LIU D,ZHANG J，et al.Lactylation of PKM2 suppresses inflammatory metabolic adaptation in pro-inflammatory macrophages［J］.Int J Biol Sci,2022,18(16):6210-6225.
［27］　WEGNER A,MEISER J,WEINDL DHILLER K.How metabolites modulate metabolic flux?［J］.Curr Opin Biotechnol,2015,34:16-22.
［28］　LITTLEWOOD-EVANS A,SARRET S,APFEL V,LOESLE P,DAWSON J,ZHANG J，et al.GPR91 senses extracellular succinate released from inflammatory macrophages and exacerbates rheumatoid arthritis［J］.J Exp Med,2016,213(9):1655-1662.
［29］　CHEN P,ZUO H,XIONG H,KOLAR M J,CHU Q,SAGHATELIAN A，et al.Gpr132 sensing of lactate mediates tumor-macrophage interplay to promote breast cancer metastasis［J］.Proc Natl Acad Sci U S A,2017,114(3):580-585.
［30］　ZHANG J,MURI J,FITZGERALD G,GORSKI T,GIANNI-BARRERA R,MASSCHELEIN E，et al.Endothelial lactate controls muscle regeneration from ischemia by inducing M2-like macrophage polarization［J］.Cell Metab,2020,31(6):1136-1153.
［31］　DISKIN C,RYAN T A J,O’NEILL L A J.Modification of proteins by metabolites in immunity［J］.Immunity,2021,54(1):19-31.
［32］　JHA A K,HUANG S C,SERGUSHICHEV A,LAMPROPOULOU V,IVANOVA Y,LOGINICHEVA E，et al.Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization［J］.Immunity,2015,42(3):419-430.
［33］　SQUADRITO M,LDE PALMA M.Macrophage regulation of tumor angiogenesis:implications for cancer therapy［J］.Mol Aspects Med,2011,32(2):123-145.
［34］　FANTIN A,VIEIRA J M,GESTRI G,DENTI L,SCHWARZ Q,PRYKHOZHIJ S，et al.Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction［J］.Blood,2010,116(5):829-840.
［35］　LIU Z,XU J,MA Q,ZHANG X,YANG Q,WANG L，et al.Glycolysis links reciprocal activation of myeloid cells and endothelial cells in the retinal angiogenic niche［J］.Sci Transl Med,2020,12(555):eaay 1371.
［36］　CONNOR K M,SANGIOVANNI J P,LOFQVIST C,ADERMAN C M,CHEN J,HIGUCHI A，et al.Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis［J］.Nat Med,2007,13(7):868-873.
［37］　BRAILEY P M,EVANS L,LPEZ-RODRGUEZ J C,SINADINOS A,TYRREL V,KELLY G，et al.CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses［J］.Nat Commun,2022,13(1):6723.
［38］　FREIGANG S,AMPENBERGER F,WEISS A,KANNEGANTI T D,IWAKURA Y,HERSBERGER M，et al.Fatty acid-induced mitochondrial uncoupling elicits inflammasome-independent IL-1α and sterile vascular inflammation in atherosclerosis［J］.Nat Immunol,2013,14(10):1045-1053.
［39］　MALANDRINO M I,FUCHO R,WEBER M,CALDERON-DOMINGUEZ M,MIR J F,VALCARCEL L，et al.Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation［J］.Am J Physiol Endocrinol Metab,2015,308(9):E756-769.
［40］　HSIEH W Y,ZHOU Q D,YORK A G,WILLIAMS K J,SCUMPIA P O,KRONENBERGER E B，et al.Toll-like receptors induce signal-specific reprogramming of the macrophage lipidome［J］.Cell Metab,2020,32(1):128-143.
［41］　BAI R,LI Y,JIAN L,YANG Y,ZHAO L,WEI M.The hypoxia-driven crosstalk between tumor and tumor-associated macrophages:mechanisms and clinical treatment strategies［J］.Mol Cancer,2022,21(1):177.
［42］　BLASIAK J,PETROVSKI G,VERB Z,FACSK AKAARNIRANTA K.Oxidative stress,hypoxia,and autophagy in the neovascular processes of age-related macular degeneration［J］.Biomed Res Int,2014,2014:768026.
［43］　MURATA K,FANG C,TERAO C,GIANNOPOULOU E G,LEE Y J,LEE M J，et al.Hypoxia-sensitive COMMD1 integrates signaling and cellular metabolism in human macrophages and suppresses osteoclastogenesis［J］.Immunity,2017,47(1):66-79.
［44］　LIU Z,MAO X,YANG Q,ZHANG X,XU J,MA Q，et al.Suppression of myeloid PFKFB3-driven glycolysis protects mice from choroidal neovascularization［J］.Br J Pharmacol,2022,179(22):5109-5131.
［45］　MINHAS P S,LATIF-HERNANDEZ A,MCREYNOLDS M R,DURAIRAJ A S,WANG Q,RUBIN A，et al.Restoring metabolism of myeloid cells reverses cognitive decline in ageing［J］.Nature,2021,590(7844):122-128.
［46］　LI P H,ZHANG R,CHENG L Q,LIU J,JCHEN H Z.Metabolic regulation of immune cells in proinflammatory microenvironments and diseases during ageing［J］.Ageing Res Rev,2020,64:101165.
［47］　HATA M,ANDRIESSEN E M M A,HATA M,DIAZ-MARIN R,FOURNIER F,CRESPO-GARCIA S，et al.Past history of obesity triggers persistent epigenetic changes in innate immunity and exacerbates neuroinflammation［J］.Science,2023,379(6627):45-62.
［48］　LAMBERT V,HANSEN S,SCHOUMACHER M,LECOMTE J,LEENDERS J,HUBERT P，et al.Pyruvate dehydrogenase kinase/lactate axis:a therapeutic target for neovascular age-related macular degeneration identified by metabolomics［J］.J Mol Med,2020,98(12):1737-1751.
［49］　SENE A,KHAN A A,COX D,NAKAMURA R E,SANTEFORD A,KIM B M，et al.Impaired cholesterol efflux in senescent macrophages promotes age-related macular degeneration［J］.Cell Metab,2013,17(4):549-561.
［50］　GONG Y,TOMITA Y,EDIN M L,REN A,KO M,YANG J，et al.Cytochrome P450 oxidase 2J inhibition suppresses choroidal neovascularization in mice［J］.Metabolism,2022,134:155266.
［51］　WIEGHOFER P,HAGEMEYER N,SANKOWSKI R,SCHLECHT A,STASZEWSKI O,AMANN L，et al.Mapping the origin and fate of myeloid cells in distinct compartments of the eye by single-cell profiling［J］.EMBO J,2021,40(6):e105123.
［52］　LCKOFF A,SCHOLZ R,SENNLAUB F,XU HLANGMANN T.Comprehensive analysis of mouse retinal mononuclear phagocytes［J］.Nat Protoc,2017,12(6):1136-1150.
［53］　SUN C,LI T,SONG X,HUANG L,ZANG Q,XU J，et al.Spatially resolved metabolomics to discover tumor-associated metabolic alterations［J］.Proc Natl Acad Sci U S A,2019,116(1):52-57.
［54］　MILLER A,NAGY C,KNAPP B,LAENGLE J,PONWEISER E,GROEGER M，et al.Exploring metabolic configurations of single cells within complex tissue microenvironments［J］.Cell Metab,2017,26(5):788-800.
［55］　KHODAEI T,INAMDAR S,SURESH A,PACHARYA A P.Drug delivery for metabolism targeted cancer immunotherapy［J］.Adv Drug Delivery Rev,2022,184:114242.

相似文献/References:

[1]高翔,王雨生. 免疫相关的巨噬细胞和髓样血管生成细胞在视网膜新生血管发生发展中的作用[J].眼科新进展,2014,34(7):687.[doi:10.13389/j.cnki.rao.2014.0189]
[2]高翔,王雨生. 巨噬细胞在小鼠氧诱导视网膜新生血管形成中的作用[J].眼科新进展,2015,35(3):201.[doi:10.13389/j.cnki.rao.2015.0055]
　GAO Xiang,WANG Yu-Sheng. Role of macrophages in oxygen-induced retinal neovas-cularization in mice[J].Recent Advances in Ophthalmology,2015,35(11):201.[doi:10.13389/j.cnki.rao.2015.0055]
[3]伍雪,张锐.葡萄膜黑色素瘤相关炎症浸润细胞及免疫治疗[J].眼科新进展,2019,39(3):282.[doi:10.13389/j.cnki.rao.2019.0064]
　WU Xue,ZHANG Rui.Inflammatory infiltrating cells related to uveal melanoma and its immunotherapy[J].Recent Advances in Ophthalmology,2019,39(11):282.[doi:10.13389/j.cnki.rao.2019.0064]
[4]陈雨晴,简守珺,岳娟,等.高糖饮食对小鼠真菌性角膜炎的影响[J].眼科新进展,2019,39(4):301.[doi:10.13389/j.cnki.rao.2019.0068]
　CHEN Yu-Qing,JIAN Shou-Jun,YUE Juan,et al.The effect of high-fructose diet on the course of fungal keratitis in mice[J].Recent Advances in Ophthalmology,2019,39(11):301.[doi:10.13389/j.cnki.rao.2019.0068]
[5]李东辉,龙琴,王静怡,等.后部巩膜F4/80和CD206阳性巨噬细胞在小鼠形觉剥夺性近视发生发展中的变化[J].眼科新进展,2019,39(12):1116.[doi:10.13389/j.cnki.rao.2019.0256]
　LI Dong-Hui,LONG Qin,WANG Jing-Yi,et al.Changes in F4/80 and CD206 positive macrophages in posterior sclera in the development of form-deprivation myopia of mice[J].Recent Advances in Ophthalmology,2019,39(11):1116.[doi:10.13389/j.cnki.rao.2019.0256]

备注/Memo

备注/Memo:
国家自然科学基金（编号：82171076，82101257）；上海市科学技术委员会项目（编号：20Z11900400，21YF1436900）
更新日期/Last Update: 2023-11-05