脈絡(luò)膜新生血管階段一CNV得發(fā)生機(jī)制RPE-Bruch膜-脈絡(luò)膜毛細(xì)血管復(fù)合體改變對(duì)CNV得影響C57BL/6J(B6)Laser-inducedCNV腹腔麻醉:0、5%戊巴比妥鈉散瞳:托品酰胺苯腎上腺素激光:647、1nm;50mmspotsize;0、05sduration;360mW、1PD;3,6,9,12o’clockpositionsFundusfluoresceinangiography3minafterintraperitonealinjectionof0、3mLof2%fluoresceinsodiumwasinjectedintotheintraperitonealcavityofthemice、細(xì)胞名稱(chēng)細(xì)胞株內(nèi)皮細(xì)胞themurinecelllineb-End3;humanumbilicalveinendothelialcells;Choroid-retinal

endothelialcellline

RPEhumancelllineARPE-19; 巨噬細(xì)胞themurinecelllineRAW264、7新生血管形成過(guò)程內(nèi)皮細(xì)胞得活化(缺氧)(HIF-1)VEGFNO(血管舒張);

內(nèi)皮細(xì)胞通透性增加,有利于血漿向組織擴(kuò)散血管外基質(zhì)得降解內(nèi)皮細(xì)胞得增生、移行

新生血管得成熟VEGF,bFGFT-PA,u-PATNF-a,IL-1MMP-1,MMP-3上調(diào)VEGFNOcGMPMAPKbFGF,整合素avB3等PDGF,aFGF,Ang及受體Tie-1,Tie-2RPE對(duì)CNV得雙重調(diào)節(jié)功能1、促進(jìn)作用生成促進(jìn)血管內(nèi)皮細(xì)胞增生與移行得VEGF,FGF,TGF-a,TNF-a等等誘導(dǎo)體內(nèi)血管內(nèi)皮細(xì)胞形成窗孔結(jié)構(gòu),影響新生血管得成熟2、抑制作用直接接觸抑制血管內(nèi)皮細(xì)胞得移行分泌抑制血管內(nèi)皮細(xì)胞生長(zhǎng)得物質(zhì):TGF-b,PEDF

釋放凝血酶原激活物抑制因子,使纖維酶原向纖溶酶得轉(zhuǎn)化受阻,細(xì)胞外基質(zhì)不能降解巨噬細(xì)胞

激光誘導(dǎo)CNV,第一天巨噬細(xì)胞出現(xiàn),第三天達(dá)到高峰,5-7天后開(kāi)始減少。VEGF,MMP-9蛋白水解酶(玻璃膜)IL-1a,IL-1b,TNF-aIL-8,MCP-1生成血管活性因子巨噬細(xì)胞+RPE參與血管內(nèi)皮生長(zhǎng)因子誘發(fā)脈絡(luò)膜新生血管得信號(hào)通路MAPK途徑PI-3K-AKt/PKB途徑鈣離子依賴(lài)性激酶途徑NO途徑P38內(nèi)皮細(xì)胞移行VEGF誘導(dǎo)活化:ERK,JNK大家學(xué)習(xí)辛苦了,還就是要堅(jiān)持繼續(xù)保持安靜PI-3K:CEC增生ILK:內(nèi)皮細(xì)胞增生與移行轉(zhuǎn)錄因子STAT3NF-kappa-BHIF-1STAT3Signaltransducerandtranscriptionactivator

退化期CNV得RPE細(xì)胞中,有STAT3得高表達(dá),而在已纖維化得盤(pán)狀瘢痕中,STAT3得表達(dá)呈陰性,提示STAT3得活化與CNV得纖維化有關(guān)。STAT3+CNV1、AnovelprotectiverolefortheinnateimmunityToll-LikeReceptor3(TLR3)intheretinaviaStat3、MolCellNeurosci、2014Sep28;63C:38-48IF:3、732、CNTF-mediatedprotectionofphotoreceptorsrequiresinitialactivationofthecytokinereceptorgp130inMüllerglialcells、ProcNatlAcadSciUSA、2013Nov19;110(47):E4520-9IF:9、813、Toll-likereceptor3(TLR3)protectsretinalpigmentedepithelium(RPE)cellsfromoxidativestressthroughaSTAT3-dependentmechanism、MolImmunol、2013Jun;54(2):122-31IF:3、04、SuppressionofchoroidalneovascularizationthroughinhibitionofAPE1/Ref-1redoxactivity、InvestOphthalmolVisSci、2014Jun26;55(7):4461-9IF、3、66

5、IL-27inhibitspathophysiologicalintraocularneovascularizationduetolaserburn、JLeukocBiol、2012Feb;91(2):267-73IF:4、36、Interleukin-6receptor-mediatedactivationofsignaltransducerandactivatoroftranscription-3(STAT3)promoteschoroidalneovascularization、AmJPathol、2007Jun;170(6):2149-58IF:4、67、Hyperglycaemiaexacerbateschoroidalneovascularisationinmiceviatheoxidativestress-inducedactivationofSTAT3

signallingin

RPE

cells、PLoSOne、2012;7(10):e47600、doi:10、1371/journal、pone、0047600、Epub2012Oct19NF-kappa-BNFKBisatranscriptionregulatorthatisactivatedbyvariousintra-andextra-cellularstimulisuchascytokines,oxidant-freeradicals,ultravioletirradiation,andbacterialorviralproducts、ActivatedNFKBtranslocatesintothenucleusandstimulatestheexpressionofgenesinvolvedinawidevarietyofbiologicalfunctions、InappropriateactivationofNFKBhasbeenassociatedwithanumberofinflammatorydiseaseswhilepersistentinhibitionofNFKBleadstoinappropriateimmunecelldevelopmentordelaye