脈絡膜新生血管CNVCNV的發生機制RPE-Bruch膜-脈絡膜毛細血管復合體改變對CNV的影響Fundusfluoresceinangiography3minafterintraperitonealinjectionof0.3mLof2%fluoresceinsodiumwasinjectedintotheintraperitonealcavityofthemice.細胞名稱細胞株內皮細胞themurinecelllineb-End3;humanumbilicalveinendothelialcells;Choroid-retinalendothelialcellline

RPEhumancelllineARPE-19; 巨噬細胞themurinecelllineRAW264.7新生血管形成過程內皮細胞的活化（缺氧）(HIF-1)VEGFNO(血管舒張);內皮細胞通透性增加，有利于血漿向組織擴散血管外基質的降解內皮細胞的增生、移行

新生血管的成熟VEGF,bFGFT-PA,u-PATNF-a,IL-1MMP-1,MMP-3上調VEGFNOcGMPMAPKbFGF,整合素avB3等PDGF,aFGF,Ang及受體Tie-1,Tie-2RPE對CNV的雙重調節功能1.促進作用生成促進血管內皮細胞增生和移行的VEGF,FGF,TGF-a,TNF-a等等誘導體內血管內皮細胞形成窗孔結構，影響新生血管的成熟2.抑制作用直接接觸抑制血管內皮細胞的移行分泌抑制血管內皮細胞生長的物質：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的轉化受阻，細胞外基質不能降解參與血管內皮生長因子誘發脈絡膜新生血管的信號通路MAPK途徑PI-3K-AKt/PKB途徑鈣離子依賴性激酶途徑NO途徑PI-3K:CEC增生ILK：內皮細胞增生和移行轉錄因子STAT3NF-kappa-BHIF-1STAT3Signaltransducerandtranscriptionactivator

退化期CNV的RPE細胞中，有STAT3的高表達，而在已纖維化的盤狀瘢痕中，STAT3的表達呈陰性，提示STAT3的活化與CNV的纖維化有關。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.InappropriateactivationofNFKBhasbeenassociatedwithanumberofinflammatorydiseaseswhilepersistentinhibitionofNFKBleadstoinappropriateimmunecelldevelopmentordelayedcellgrowth.

NFκB受多種細胞內和細胞外的刺激如細胞因子，氧化劑自由基，紫外線照射，細菌性或病毒性產物激活的轉錄調節子。激活的NFκB易位到細胞核中，并刺激參與多種生物功能的基因的表達。NFκB的不適當活化已經與許多炎癥性疾病相關，而NFKB的持久性抑制導致不適當的免疫細胞的發育或延緩細胞生長。

HIF-1

Functionsasamastertranscriptionalregulatoroftheadaptiveresponsetohypoxia.Underhypoxicconditions,activatesthetranscriptionofover40genes,includingerythropoietin,glucosetransporters,glycolyticenzymes,vascularendothelialgrowthfactor,HILPDA,andothergeneswhoseproteinproductsincreaseoxygendeliveryorfacilitatemetabolicadaptationtohypoxia.Playsanessentialroleinembryonicvascularization,tumorangiogenesisandpathophysiologyofischemicdisease.

缺氧適應性反應的主轉錄調節。在缺氧條件下，激活了40個基因，包括促紅細胞生成素，葡萄糖轉運，糖酵解酶，血管內皮生長因子，乳過氧化物酶，和其他基因，其蛋白產物增加氧氣傳遞或促進代謝適應低氧的轉錄。在胚胎血管生成，腫瘤血管生成和缺血性疾病的病理生理學中起重要作用。

HIF-11.Decorininhibitsangiogenicpotentialofchoroid-retinalendothelialcellsbydownregulatinghypoxia-inducedMet,Rac1,HIF-1αandVEGFexpressionincoculturedretinalpigmentepithelialcells.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-1α-VEGFsignalingontheangiogenesisofchoroidalneovascularizationunderhypoxicconditions.PLoSOne.2011Apr19;6(4):e18481IF:3.535.Inhibitor