Choroidal neovascularization (CNV) is an acknowledged pathogenic mechanism of various ocular diseases, and in situ cells and mobilized bone marrow-derived cells (BMCs) are thought to participate in this process. We aimed to evaluate the roles of integrin α5 in BMCs and vascular endothelial cells (VECs) in the CNV process mediated by SDF-1/CXCR4 signaling. Adult wild-type mice were engrafted with whole BMCs obtained from GFP transgenic mice and then laser injured to induce CNV. BMCs and RF/6A cells were cultured to discover the mechanism of CNV in vitro. BMCs were mobilized to CNV areas, which expressed elevated SDF-1 and CXCR4. When SDF-1 was intravitreally injected, the number of BMCs was profoundly increased. In the SDF-1-treated group, the levels of integrin α5 expressed on BMCs and VECs were significantly higher than those on the cells in the control group. SDF-1 significantly increased the expression and positive ratio of integrin α5, which was involved in the recruitment and differentiation of BMCs into BMC-derived VECs, and these effects were suppressed by the CXCR4 inhibitor AMD3100. The PI3K/AKT pathway rather than the ERK pathway mediated SDF-1/CXCR4 induction of integrin α5. Integrin α5 suppression efficiently prevented the production of TGF-β and bFGF but not VEGF. Inhibiting the SDF-1/CXCR4-PI3K/AKT-integrin α5 axis reduced CNV severity. Integrin α5 participates in BMC recruitment and differentiation in SDF-1/CXCR4-induced CNV and inhibition of this pathway may be a new approach to inhibit CNV.

脉络膜新生血管形成（CNV）是各种眼部疾病的公认致病机制，据认为原位细胞和动员的骨髓衍生细胞（BMC）参与了该过程。我们旨在评估整合素α5在BMC和血管内皮细胞（VEC）在由SDF-1 / CXCR4信号介导的CNV过程中的作用。将成年野生型小鼠植入从GFP转基因小鼠中获得的完整BMC，然后激光损伤以诱导CNV。培养BMC和RF / 6A细胞以发现CNV的体外机制。BMC被动员到CNV区域，该区域表达SDF-1和CXCR4升高。玻璃体内注射SDF-1时，BMC的数量大大增加。在用SDF-1处理的组中，在BMC和VEC上表达的整联蛋白α5的水平显着高于对照组中的细胞。SDF-1显着增加了整合素α5的表达和阳性比率，这与将BMC募集和分化为BMC衍生的VEC有关，而CXCR4抑制剂AMD3100抑制了这些作用。PI3K / AKT途径而非ERK途径介导整合素α5的SDF-1 / CXCR4诱导。整联蛋白α5抑制有效地阻止了TGF-β和bFGF的产生，但不能阻止VEGF的产生。抑制SDF-1 / CXCR4-PI3K / AKT整合素α5轴可降低CNV严重程度。