Effects Of IL-10 And Flt3 On Retinal Neovascularization

Part one:Investigation of Interleukin 10 regulates macrophages and promotes ocular neovascularization.Objective:Interleukin 10(IL-10),also known as human cytokine synthesis inhibitory factor,is an anti-inflammatory cytokine.In this study,the effects of IL-10 on ocular neovascularization(NV)were deeply investigated.Methods:The expression of IL10 was investigated in mice with ischemic retinopathy and in transgenic mice with the expression of vascular endothelial growth factor(VEGF)in photoreceptors.Mice deficient in IL-10 were used to test the effect of IL 10 on RNV and CNVResults:Mice deficient in IL-10 exhibited a significant reduction area of NV in ROP and CNV mouse models.Mice lacking IL-10 showed reduced levels of HIF-1? and the suppression of the ischemia-induced expression of VEGF and of VEGF receptorl(VEGFR1).Mfs were regulated and reduced in the ischemic retina of mice with IL-10 deficiency.Conclusion:IL-10 stimulates ocular NV through the modulation of HIF-1? and its target genes,VEGF and VEGFR1.IL-10 promotes ocular NV via the Mf porarization change response to retina ischemiaPart two:The effects of Flt3 on ocular neovascularization and the investigation of its mechanism.Objective:Fms-like Tyrosine Kinase 3(Flt3)also called FLK2,play an important role in proliferation,differentiation and apoptosis of hematopoietic stem cells,precursor B cells,dendritic cells and natural killer cells.In this study the effect of Flt3 on ocular NV was investigated,and the effect of AC220,a novel antagonist of Flt3,inhibiting ocular NV was investigated.Methods:Expression of Flt3 was investigated in mice with ischemic retinopathy,rho/VEGF transgenic,CNV and rhO/rtTA-TRE/VEGF double transgenic mice.Mice deficient in Flt3 were used to test the effect of Flt3 on RNV and CNV.The anti-angiogemc activity and Mf polarization of AC220 were investigated by intravitreous administration in mice model with ROP.CNV,sub-RNV.Results:Mice deficient in Flt3 showed a significant reduction in ischemia-induced RNV,CNV at rupture sites in Bruch's membrane.Expression level of retinal Flt3 was higher in ROP group than that in normal group.AC220 had anti-angiogenic activity in RNV,CNV and VEGF-induced sub-retinal NV when administrated with an intravitreous injection,and significantly reduced(P<0.05)total retinal detachment(TRD)in double transgenic mice with inducible over-expression of VEGF in photoreceptors(rho/rtTA-TRE/VEGF).Conclusion:Flt3 has a close relationship with ROP.AC220 was shown to have anti-angiogenic activity in ROP and can adjust the polarization of Mf.Antagonists of Flt3 could be a subsidiary therapeutic medicine of VEGF inhibitors.