Effect of Notch1-Dll4 signaling pathway in mouse model of oxygen-induced retinopathy

Objective: To investigate the role of Notch1-Dll4 signaling pathway in the retinal neovascularization of oxygen-induced retinopathy mouse model. Methods: Thirty C57BL/6J mouse pups in experimental group were exposed to (75 +/- 2)% oxygen for 5 d and then returned to room air. Another 30 mice in control group were subjected to room air. The expression of retinal Dll4, vascular endothelial growth factor 1 (VEGFR-1) and VEGFR-2 was measured by immunohistochemical analysis and RT-PCR. Results: In both groups, Dll4, VEGFR-1 and VEGFR-2 proteins were expressed in retina. In 17-d-old (P17) mice, positive rate of VEGFR-1 in experimental group was significantly lower than that in control group (P< 0.05). Positive rate of VEGFR-2 did not significantly differ between two groups (all P> 0.05). At P12 and P17, positive rates of Dll4 considerably differed between two groups (both P< 0.05). In experimental group, positive rates of VEGFR-1 and Dll4 tended to decline over time (both P< 0.001), whereas an increasing tendency for VEGFR-2 (P< 0.05). In control group, positive rate of VEGFR-1 tended to decrease, whereas VEGFR-2 tended to elevate over time (P< 0.001). VEGFR-1 mRNA expression significantly differed between two groups at P17 (P< 0.05). VEGFR-2 mRNA did not dramatically differ between two groups (all P> 0.05). The expression of Dll4 mRNA significantly differed between two groups at P12 and P17 (both P< 0.05). In experimental group, the expression of VEGFR-1 and Dll4 proteins declined (both P< 0.05), whereas VEGFR-2 protein was elevated over time (P< 0.05). In control group, the expression of VEGFR-2 protein was significantly up-regulated over time (P< 0.05), whereas no changes for VEGFR-1 and Dll4 proteins (both P> 0.05). Dll4 expression was positively correlated with VEGFR-1 (r= 0.905, P< 0.001). Conclusion: Dll4 and VEGFR-1 expression were both inhibited during neovascularization, and Dll4 expression positively correlated with Dll4 expression. Notch1-Dll4 signaling pathway was probably involved in retinal neovascularization.