脉络膜新生血管（CNV）的"定向侵袭"机制复杂且少有报道。课题组前期研究发现integrinα5β1能独立于VEGF/VEGFR通路之外，单独或协同VEGF/VEGFR通路，诱导形成CNV侵袭，且不被VEGF抗体所抑制；新近发现Slit3/Robo4信号参与调控内皮细胞定向迁移，介导新生血管形成，提示Slit3/Robo4可能是integrinα5β1介导的CNV"定向侵袭"的上游调控信号之一。以此为基础，课题组拟在体内外CNV模型中，采用基因过表达/沉默技术,研究Slit3/Robo4信号对integrinα5β1通路表达影响，及对脉络膜血管内皮细胞迁移、侵袭、管腔形成的影响，及其探讨其参与CNV"定向侵袭"的分子机制，阐明Slit3/Robo4-integrinα5β1活化是CNV"定向侵袭"的重要调控机制之一；为我们进一步认识CNV形成机制，为提高抗VEGF治疗临床疗效提供理论依据。

The mechanism of choroidal neovascularization invation was complicate and rarely reported. Our previous research revealed that integrinα5β1 can be singled out as one of the primary proteins required for CNV as a VEGF-independent pathway, which may explain why anti-VEGF monothreapy doesn't work in some cases. Recently, it was found that neuronal guidance signal Slit3/Robo4 pathway participated into regulation of endothelial cell migration and angiogenesis. So it suggested that Slit3/Robo4 pathway might play a key role in the regulation of integrinα5β1 pathway mediated CNV invasion. Therefore, activation/inhibition of Slit3/Robo4 pathway will be investigated by construction Robo4 gene overexpression and silence plasmid to explore whether Slit3/Robo4 is the upstream regulatory pathway involving in integrinα5β1-mediated CNV invastion.The effector of Robo4-integrionα5β1 binding on choroidal endothelial cell migration,invasion, tube formation will also be explored by overexpression/inhibition Robo4 gene. In conclusion, the critical molecular and its mechanism in CNV directional invasion will be investigated to test its therapeutic potential in CNV diseases in this research.