脉络膜新生血管阶段一

脉络膜新生血管CNV CNV的发生机制 RPE Bruch膜 脉络膜毛细血管复合体改变对CNV的影响 C57BL 6J B6 Laser inducedCNV 腹腔麻醉 0 5 戊巴比妥钠散瞳 托品酰胺苯肾上腺素激光 647 1nm 50mmspotsize 0 05sduration 360mW 1PD 3 6 9 12o clockpositions Fundusfluoresceinangiography 3minafterintraperitonealinjectionof0 3mLof2 fluoresceinsodiumwasinjectedintotheintraperitonealcavityofthemice 细胞 新生血管形成过程 内皮细胞的活化 缺氧 HIF 1 VEGFNO 血管舒张 内皮细胞通透性增加 有利于血浆向组织扩散血管外基质的降解内皮细胞的增生 移行新生血管的成熟 VEGF bFGF T PA u PA TNF a IL 1 MMP 1 MMP 3 上调 VEGF NOcGMP MAPK bFGF 整合素avB3等 PDGF aFGF Ang及受体Tie 1 Tie 2 RPE对CNV的双重调节功能 1 促进作用生成促进血管内皮细胞增生和移行的VEGF FGF TGF a TNF a等等诱导体内血管内皮细胞形成窗孔结构 影响新生血管的成熟2 抑制作用直接接触抑制血管内皮细胞的移行分泌抑制血管内皮细胞生长的物质 TGF b PEDF释放凝血酶原激活物抑制因子 使纤维酶原向纤溶酶的转化受阻 细胞外基质不能降解 巨噬细胞 激光诱导CNV 第一天巨噬细胞出现 第三天达到高峰 5 7天后开始减少 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 巨噬细胞 RPE 参与血管内皮生长因子诱发脉络膜新生血管的信号通路 MAPK途径PI 3K AKt PKB途径钙离子依赖性激酶途径NO途径 P38内皮细胞移行 VEGF诱导活化 ERK JNK PI 3K CEC增生 ILK 内皮细胞增生和移行 转录因子 STAT3NF kappa BHIF 1 STAT3 Signaltransducerandtranscriptionactivator退化期CNV的RPE细胞中 有STAT3的高表达 而在已纤维化的盘状瘢痕中 STAT3的表达呈阴性 提示STAT3的活化与CNV的纤维化有关 STAT3 CNV 1 AnovelprotectiverolefortheinnateimmunityToll LikeReceptor3 TLR3 intheretinaviaStat3 MolCellNeurosci 2014Sep28 63C 38 48IF 3 732 CNTF mediatedprotectionofphotoreceptorsrequiresinitialactivationofthecytokinereceptorgp130inM llerglialcells 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 3 665 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 inducedactivationofSTAT3signallinginRPEcells PLoSOne 2012 7 10 e47600 doi 10 1371 journal pone 0047600 Epub2012Oct19 NF kappa B NFKBisatranscriptionregulatorthatisactivatedbyvariousintra andextra cellularstimulisuchascytokines oxidant freeradicals ultravioletirradiation andbacterialorviralproducts ActivatedNFKBtranslocatesintothenucleusandstimulatestheexpressionofgenesinvolvedinawidevarietyofbiologicalfunctions InappropriateactivationofNFKBhasbeenassociatedwithanumberofinflammatorydiseaseswhilepersistentinhibitionofNFKBleadstoinappropriateimmunecelldevelopmentordelayedcellgrowth NF B受多种细胞内和细胞外的刺激如细胞因子 氧化剂自由基 紫外线照射 细菌性或病毒性产物激活的转录调节子 激活的NF B易位到细胞核中 并刺激参与多种生物功能的基因的表达 NF B的不适当活化已经与许多炎症性疾病相关 而NFKB的持久性抑制导致不适当的免疫细胞的发育或延缓细胞生长 NF kappa B 1 Rolesfortheubiquitin proteasomepathwayinproteinqualitycontrolandsignalingintheretina implicationsinthepathogenesisofage relatedmaculardegeneration MolAspectsMed 2012Aug 33 4 446 66IF 10 32 Macularpigmentluteinisantiinflammatoryinpreventingchoroidalneovascularization ArteriosclerThrombVascBiol 2007Dec 27 12 2555 62IF 5 533 IKK2inhibitionattenuateslaser inducedchoroidalneovascularization PLoSOne 2014 9 1 e87530IF 3 534 TNF decreasesVEGFsecretioninhighlypolarizedRPEcellsbutincreasesitinnon polarizedRPEcellsrelatedtocrosstalkbetweenJNKandNF Bpathways PLoSOne 2013 8 7 e69994IF 3 535 NLRP3inflammasomeactivationinretinalpigmentepithelialcellsbylysosomaldestabilization implicationsforage relatedmaculardegeneration InvestOphthalmolVisSci 2013Jan7 54 1 110 20IF 3 666 RegulatoryroleofHIF 1alphainthepathogenesisofage relatedmaculardegeneration AMD AgeingResRev 2009Oct 8 4 349 58IF 7 637 RolesofNF B miR 29s MMP 2circuitryinexperimentalchoroidalneovascularization JNeuroinflammation 2014May15 11 88IF 4 9 HIF 1 Functionsasamastertranscriptionalregulatoroftheadaptiveresponsetohypoxia Underhypoxicconditions activatesthetranscriptionofover40genes includingerythropoietin glucosetransporters glycolyticenzymes vascularendothelialgrowthfactor HILPDA andothergeneswhoseproteinproductsincreaseoxygendeliveryorfacilitatemetabolicadaptationtohypoxia Playsanessentialroleinembryonicvascularization tumorangiogenesisandpathophysiologyofischemicdisease 缺氧适应性反应的主转录调节 在缺氧条件下 激活了40个基因 包括促红细胞生成素 葡萄糖转运 糖酵解酶 血管内皮生长因子 乳过氧化物酶 和其他基因 其蛋白产物增加氧气传递或促进代谢适应低氧的转录 在胚胎血管生成 肿瘤血管生成和缺血性疾病的病理生理学中起重要作用 HIF 1 1 Decorininhibitsangiogenicpotentialofchoroid retinalendothelialcellsbydownregulatinghypoxia inducedMet Rac1 HIF 1 andVEGFexpressionincoculturedretinalpigmentepithelialcells ExpEyeRes 2013Nov 116 151 60IF 3 022 Methallothionein 3contributestovascularendothelialgrowthfactorinductioninamousemodelofchoroidalneovascularization Metallomics 2013Oct 5 10 1387 96IF 3 983 Impactsofhypoxia induciblefactor 1knockoutintheretinalpigmentepitheliumonchoroidalneovascularization InvestOphthalmolVisSci 2012Sep14 53 10 6197 206IF 3 664 InfluenceofDll4viaHIF 1 VEGFsignalingontheangiogenesisofchoroidalneovascularizationunderhypoxicconditions PLoSOne 2011Apr19 6 4 e18481IF