[1]张甜甜,李静,田珍.血小板源性生长因子在湿性年龄相关性黄斑变性新生血管及纤维化中的作用研究进展[J].眼科新进展,2024,44(5):410-414.[doi:10.13389/j.cnki.rao.2024.0080]
　ZHANG Tiantian,LI Jing,TIAN Zhen.Advances in the role of platelet-derived growth factor in neovascularisation and fibrosis in neovascular age-related macular degeneration[J].Recent Advances in Ophthalmology,2024,44(5):410-414.[doi:10.13389/j.cnki.rao.2024.0080]
点击复制

血小板源性生长因子在湿性年龄相关性黄斑变性新生血管及纤维化中的作用研究进展/HTML
分享到：

《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
44卷
期数:
2024年5期
页码:
410-414
栏目:
文献综述
出版日期:
2024-04-30

文章信息/Info

Title:
Advances in the role of platelet-derived growth factor in neovascularisation and fibrosis in neovascular age-related macular degeneration
作者:
张甜甜; 李静; 田珍
710021　陕西省西安市，西安医学院（张甜甜，田珍）；710068　陕西省西安市，陕西省人民医院眼科（张甜甜，李静，田珍）
Author(s):
ZHANG Tiantian1; 2; LI Jing2; TIAN Zhen1; 2
1.Xi’an Medical University,Xi’an 710021,Shaanxi Province,China
2.Shaanxi Provincial People’s Hospital,Xi’an 710068,Shaanxi Province,China
关键词:
血小板源性生长因子; 年龄相关性黄斑变性; 黄斑区新生血管; 纤维化; 发病机制
Keywords:
platelet-derived growth factor;  age-related macular degeneration;  macular choroidal neovascularization;  fibrosis;  pathogenesis
分类号:
R774.5
DOI:
10.13389/j.cnki.rao.2024.0080
文献标志码:
A
摘要:
黄斑区脉络膜新生血管及视网膜下纤维化(SRFi)是湿性年龄相关性黄斑变性最常见的病理机制，常导致50岁以上人群不可逆性的视力丧失。尽管目前抗血管内皮生长因子已经成为临床主要有效的一线用药，但仍有近50%的病例因SRFi产生的瘢痕而最终视力丧失。血小板源性生长因子家族是从人血小板中分离出来的一类促血管生成因子，目前已证实其参与了黄斑区脉络膜新生血管形成的过程，但具体作用机制仍不清楚。本文将血小板源性生长因子在年龄相关性黄斑变性新生血管以及SRFi形成的作用机制作一综述，为未来开发新型诊疗方式提供资料支持。
Abstract:
Macular choroidal neovascularization (MNV) and subretinal fibrosis (SRFi) are the most common pathomechanisms of neovascular age-related macular degeneration (nAMD), which often lead to irreversible vision loss in people over 50 years of age. Even though there is an effective clinical medication known as anti-vascular endothelial growth factor (VEGF), nearly 50% of patients lose vision due to scars produced by SRFi. Platelet-derived growth factors (PDGF) are pro-angiogenic factors isolated from human platelets. It has been known that they play a role in choroidal neovascularization in the macula, but the specific mechanism of action remains unclear. This article reviews the mechanism of PDGF in neovascularization and SRFi formation in nAMD, providing data for the future development of new diagnostic and therapeutic methods.

参考文献/References:

［1］　THOMAS C J,MIRZA R G,GILL M K.Age-related macular degeneration［J］.Med Clin North Am,2021,105(3):473-491.
［2］　KLINKHAMMER B M,FLOEGE J,BOOR P.PDGF in organ fibrosis［J］.Mol Aspects Med,2018,62:44-62.
［3］　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.Alteration of cytokine expression in exudative age-related macular degeneration and its targeting therapy［J］.Chin J Exp Ophthalmol,2015,33(1):93-96.
［4］　ZEHETNER C,KIRCHMAIR R,NEURURER S B,KRALINGER M T,BECHRAKIS N E,KIESELBACH G F.Systemic upregulation of PDGF-B in patients with neovascular AMD［J］.Invest Ophthalmol Vis Sci,2014,55(1):337-344.
［5］　LIU Y,NODA K,MURATA M,WU D,KANDA A,ISHIDA S.Blockade of platelet-derived growth factor signaling inhibits choroidal neovascularization and subretinal fibrosis in mice［J］.J Clin Med,2020,9(7):2242.
［6］　CASALINO G,STEVENSON M R,BANDELLO F,CHAKRAVARTHY U.Tomographic biomarkers predicting progression to fibrosis in treated neovascular age-related macular degeneration:a multimodal imaging study［J］.Ophthalmol Retina,2018,2(5):451-461.
［7］　KAZLAUSKAS A.PDGFs and their receptors［J］.Gene,2017,614:1-7.
［8］　LU W,LI X.PDGFs and their receptors in vascular stem/progenitor cells:functions and therapeutic potential in retinal vasculopathy［J］.Mol Aspects Med,2018,62:22-32.
［9］　ANDRAE J,GALLINI R,BETSHOLTZ C.Role of platelet-derived growth factors in physiology and medicine［J］.Genes Dev,2008,22(10):1276-1312.
［10］　LI R,MAMINISHKIS A,WANG F E,MILLER S S.PDGF-C and-D induced proliferation/migration of human RPE is abolished by inflammatory cytokines［J］.Invest Ophthalmol Vis Sci,2007,48(12):5722-5732.
［11］　KUMAR A,LI X.PDGF-C and PDGF-D in ocular diseases［J］.Mol Aspects Med,2018,62:33-43.
［12］　解鹏亮,郑陆芳,董明霞,董如娇,陈芳.血清VEGF、PDGF和ES水平与湿性年龄相关性黄斑变性的关系［J］.分子诊断与治疗杂志,2021,13(10):1631-1634.
XIE P L,ZHENG L F,DONG M X,DONG R J,CHEN F.Serum levels of VEGF,PDGF and ES in relation to wet age-related macular degeneration［J］.J Mol Diagn Ther,2021,13(10):1631-1634.
［13］　PARK D Y,LEE J,KIM J,KIM K,HONG S,HAN S,et al.Plastic roles of pericytes in the blood-retinal barrier［J］.Nat Commun,2017,8:15296.
［14］　HOU X,KUMAR A,LEE C,WANG B,ARJUNAN P,DONG L,et al.PDGF-CC blockade inhibits pathological angiogenesis by acting on multiple cellular and molecular targets［J］.Proc Natl Acad Sci U S A,2010,107(27):12216-12221.
［15］　SMYTH L C D,HIGHET B,JANSSON D,WU J,RUSTENHOVEN J,AALDERINK M,et al.Characterisation of PDGF-BB:PDGFRβ signalling pathways in human brain pericytes:evidence of disruption in Alzheimer’s disease［J］.Commun Biol,2022,5(1):235.
［16］　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.
［17］　LUO X,YANG S,LIANG J,ZHAI Y,SHEN M,SUN J,et al.Choroidal pericytes promote subretinal fibrosis after experimental photocoagulation［J］.Dis Model Mech,2018,11(4):dmm032060.
［18］　GACEB A,ZEN I,PADEL T,BARBARIGA M,PAUL G.Pericytes secrete pro-regenerative molecules in response to platelet-derived growth factor-BB［J］.J Cereb Blood Flow Metab,2018,38(1):45-57.
［19］　IMHOF B A,BALLET R,HAMMEL P,JEMELIN S,GARRIDO-URBANI S,IKEYA M,et al.Olfactomedin-like 3 promotes PDGF-dependent pericyte proliferation and migration during embryonic blood vessel formation［J］.FASEB J,2020,34(11):15559-15576.
［20］　THIJSSEN V L,PAULIS Y W,NOWAK-SLIWINSKA P,DEUMELANDT K L,HOSAKA K,SOETEKOUW P M,et al.Targeting PDGF-mediated recruitment of pericytes blocks vascular mimicry and tumor growth［J］.J Pathol,2018,246(4):447-458.
［21］　O’LEARY F,CAMPBELL M.The blood-retina barrier in health and disease［J］.FEBS J,2023,290(4):878-891.
［22］　TANG B,GONG J P,SUN J M,LUO W J,CHEN Y K,LIU Z J,et al.Construction of a plasmid for expression of rat platelet-derived growth factor C and its effects on proliferation,migration and adhesion of endothelial progenitor cells［J］.Plasmid,2013,69(3):195-201.
［23］　MA J,TANG W,GU R,HU F,ZHANG L,WU J,et al.SHP-2-induced activation of c-myc is involved in PDGF-B-regulated cell proliferation and angiogenesis in RMECs［J］.Front Physiol,2020,11:555006.
［24］　HEO J,YANG H C,RHEE W J,KANG H.Vascular smooth muscle cell-derived exosomal microRNAs regulate endothelial cell migration under PDGF stimulation［J］.Cells,2020,9(3):639.
［25］　PARAMEL G V,KARADIMOU G,EREMO A G,LJUNGBERG L U,HEDIN U,OLOFSSON P S,et al.Author correction:expression of CARD8 in human atherosclerosis and its regulation of inflammatory proteins in human endothelial cells［J］.Sci Rep,2021,11(1):8852.
［26］　SHU D Y,BUTCHER E,SAINT-GENIEZ M.EMT and EndMT:emerging roles in age-related macular degeneration［J］.Int J Mol Sci,2020,21(12):4271.
［27］　BASTIAANS J,VAN MEURS J C,VAN HOLTEN-NEELEN C,NAGTZAAM N M,VAN HAGEN P M,CHAMBERS R C,et al.Thrombin induces epithelial-mesenchymal transition and collagen production by retinal pigment epithelial cells via autocrine PDGF-receptor signaling［J］.Invest Ophthalmol Vis Sci,2013,54(13):8306-8314.
［28］　JUNG J,JEONG J,HONG H S.Substance P improves MSC-mediated RPE regeneration by modulating PDGF-BB［J］.Biochem Biophys Res Commun,2019,515(4):524-530.
［29］　DONG X,HU H,FANG Z,CUI J,LIU F.CTRP6 inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration［J］.Biomed Pharmacother,2018,103:844-850.
［30］　JANG M A,LEE S J,BAEK S E,PARK S Y,CHOI Y W,KIM C D.α-Iso-cubebene inhibits PDGF-induced vascular smooth muscle cell proliferation by suppressing osteopontin expression［J］.PLoS One,2017,12(1):e0170699.
［31］　LU Q B,WAN M Y,WANG P Y,ZHANG C X,XU D Y,LIAO X,et al.Chicoric acid prevents PDGF-BB-induced VSMC dedifferentiation,proliferation and migration by suppressing ROS/NFκB/mTOR/P70S6K signaling cascade［J］.Redox Biol,2018,14:656-668.
［32］　TAN W,ZOU J,YOSHIDA S,JIANG B,ZHOU Y.The role of inflammation in age-related macular degeneration［J］.Int J Biol Sci,2020,16(15):2989-3001.
［33］　WU A L,LIU Y T,CHOU H D,CHUANG L H,CHEN K J,CHEN Y P,et al.Role of growth factors and internal limiting membrane constituents in Müller cell migration［J］.Exp Eye Res,2021,202:108352.
［34］　DAZ-LEZAMA N,WOLF A,KOCH S,PFALLER A M,BIBER J,GUILLONNEAU X,et al.PDGF receptor alpha signaling is key for Müller cell homeostasis functions［J］.Int J Mol Sci,2021,22(3):1174.
［35］　HELDIN C H,OSTMAN A,RNNSTRAND L.Signal transduction via platelet-derived growth factor receptors［J］.Biochim Biophys Acta,1998,1378(1):F79-F113.
［36］　SUN Y,SONG R,AI Y,ZHU J,HE J,DANG M,et al.APOE2 promotes the development and progression of subretinal neovascularization in age-related macular degeneration via MAPKs signaling pathway［J］.Saudi J Biol Sci,2020,27(10):2770-2777.
［37］　司艳芳,王君,关娟,韩泉洪,惠延年.α-平滑肌肌动蛋白在PVR增生膜中的表达以及PDGF对其在人RPE细胞中表达的影响［J］.眼科新进展,2012,32(11):1010-1013.
SI Y F,WANG J,GUAN J,HAN Q H,HUI Y N.Expressions of α-smooth muscle actin in PVR and effects of PDGF on its expression in human RPE cells［J］.Rec Adv Ophthalmol,2012,32(11):1010-1013.
［38］　李秋霞,罗茂林,李茹柳,陈蔚文.紧密连接蛋白ZO-1研究概述［J］.广州中医药大学学报,2007,24(6):523-526.
LI Q X,LUO M L,LI R L,CHEN W W.Overview of tight junction protein ZO-1［J］.J Guangzhou Univ Tradit Chin Med,2007,24(6):523-526.
［39］　LI M,ZHU H,HU X,GAO F,HU X,CUI Y,et al.TMEM98,a novel secretory protein,promotes endothelial cell adhesion as well as vascular smooth muscle cell proliferation and migration［J］.Can J Physiol Pharmacol,2021,99(5):536-548.
［40］　XU Y H,FENG Y F,ZOU R,YUAN F,YUAN Y Z.Silencing of YAP attenuates pericyte-myofibroblast transition and subretinal fibrosis in experimental model of choroidal neovascularization［J］.Cell Biol Int,2022,46(8):1249-1263.
［41］　OSMAN I,DONG K,KANG X,YU L,XU F,AHMED A S I,et al.YAP1/TEAD1 upregulate platelet-derived growth factor receptor beta to promote vascular smooth muscle cell proliferation and neointima formation［J］.J Mol Cell Cardiol,2021,156:20-32.
［42］　LI T,GUO T,LIU H,JIANG H,WANG Y.Platelet-derived growth factor-BB mediates pancreatic cancer malignancy via regulation of the Hippo/Yes-associated protein signaling pathway［J］.Oncol Rep,2021,45(1):83-94.
［43］　LU C,ZHANG Q,ZHANG H,LI X,JIANG Q,YAO J.A small molecular multi-targeting tyrosine kinase inhibitor,anlotinib,inhibits pathological ocular neovascularization［J］.Biomed Pharmacother,2021,138:111493.
［44］　SHAO W,LI X,PENG J,FAN S,LIANG M,HUANG K.Apatinib attenuates phenotypic switching of arterial smooth muscle cells in vascular remodelling by targeting the PDGF Receptor-Β［J］.J Cell Mol Med,2020,24(17):10128-10139.
［45］　KONG H,ZHANG R,JING Q,LIANG Y,ZHUO Q,LI B,et al.Intravitreal injection of EV11,a novel aryl ketone amide,inhibits choroidal neovascularization via AKT/ERK1/2 pathway［J］.Microvasc Res,2022,143:104401.
［46］　LIU Y,FENG M,CAI J,LI S,DAI X,SHAN G,et al.Repurposing bortezomib for choroidal neovascularization treatment via antagonizing VEGF-A and PDGF-D mediated signaling［J］.Exp Eye Res,2021,204:108446.
［47］　SUI A,CHEN X,SHEN J,DEMETRIADES A M,YAO Y,YAO Y,et al.Inhibiting the NLRP3 inflammasome with MCC950 ameliorates retinal neovascularization and leakage by reversing the IL-1β/IL-18 activation pattern in an oxygen-induced ischemic retinopathy mouse model［J］.Cell Death Dis,2020,11(10):901.
［48］　LI H,ZEITELHOFER M,NILSSON I,LIU X,ALLAN L,GLORIA B,et al.Development of monoclonal anti-PDGF-CC antibodies as tools for investigating human tissue expression and for blocking PDGF-CC induced PDGFRα signalling in vivo［J］.PLoS One,2018,13(7):e0201089.
［49］　HONG Y K,LEE Y C,CHENG T L,LAI C H,HSU C K,KUO C H,et al.Tumor endothelial marker 1 (TEM1/endosialin/CD248) enhances wound healing by interacting with platelet-derived growth factor receptors［J］.J Invest Dermatol,2019,139(10):2204-2214.
［50］　LEE S J,KIM S,JO D H,CHO C S,KIM S R,KANG D,et al.Specific ablation of PDGFRβ-overexpressing pericytes with antibody-drug conjugate potently inhibits pathologic ocular neovascularization in mouse models［J］.Commun Med (Lond),2021,1:58.
［51］　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.
［52］　LEE J W,HUR J,KWON Y W,CHAE C W,CHOI J I,HWANG I,et al.KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state［J］.J Hematol Oncol,2021,14(1):148.

相似文献/References:

[1]范姜砾 王雨生 张鹏.湿性年龄相关性黄斑变性患者血浆中相关抗氧化酶水平测定[J].眼科新进展,2012,32(5):000.
[2]王毅 李罗翔 李娟 曾庆华.ApoE基因缺失小鼠视网膜及Bruch膜组织形态观察[J].眼科新进展,2013,33(1):000.
[3]徐新荣 仲路 黄冰林 魏源华 周欣 王玲 王富强.年龄相关性黄斑变性血浆蛋白质组学初步研究[J].眼科新进展,2013,33(2):000.
[4]党亚龙 陈彬川 穆雅林 赵满丽 朱豫.i-MP对产生2型脉络膜新生血管的年龄相关性黄斑变性患者视力及黄斑厚度的影响[J].眼科新进展,2013,33(2):000.
[5]王毅 李罗翔 李进辉 李娟 曾庆华.血脂异常ApoE基因缺失小鼠视网膜色素上皮细胞胞浆内黑色素和脂褐素的改变[J].眼科新进展,2013,33(7):000.
[6]罗文婷 孙大卫.血管黏附蛋白-1在眼科疾病中的研究进展[J].眼科新进展,2013,33(8):000.
[7]司艳芳 王君 关娟 韩泉洪 惠延年.α-平滑肌肌动蛋白在PVR增生膜中的表达以及PDGF对其在人RPE细胞中表达的影响[J].眼科新进展,2012,32(11):000.
[8]陆秉文 吴星伟.光动力疗法治疗年龄相关性黄斑变性的研究进展[J].眼科新进展,2013,33(4):000.
[9]栾兰 姚勇.湿性年龄相关性黄斑变性的治疗进展[J].眼科新进展,2013,33(4):000.
[10]胡艳红 祁明信 郭娜 陈胜 柯发杰.渗出型年龄相关性黄斑变性患者外周血CCR3的表达[J].眼科新进展,2013,33(11):000.

备注/Memo

备注/Memo:
陕西省自然科学基金面上项目（编号：2022JM-517）；陕西省人民医院科技人才支持计划项目（编号：2021JY-37）
更新日期/Last Update: 2024-05-05