IGF-1 regulates Ang II and VEGF signaling pathways in retinal neovascularization

To investigate the effect of insulin-like growth factor (IGF)-1 on regulating the occurrence of retinal neovascularization and the expression mechanism of Angiotensin II (Ang II) and vascular endothelial factor (VEGF).

A total of 40 C57BL/6J healthy mice of either gender were selected, and randomly divided into 4 groups: control group, model group, IGF-1 overexpression carrier intervention group and IGF-1 siRNA intervention group (10 in each group). Mice in control group were fed in the air without any further processing. The mice in other 3 groups were used to build high oxygen-induced retinal neovascularization model. The vitreous cavity of mice in the model group was injected with the equal amount of normal saline, while the mice in the IGF-1 overexpression carrier intervention group were injected with 1 μl IGF-1 liposomes mixture. At the same time, IGF-1 siRNA intervention group mice were continuously injected with 1 μl IGF-1 siRNA liposomes mixture for 3d. Stretched preparation of retina was used to observe the neovascularization form; HE staining tissue section were prepared to observe the amount of vascular endothelial nuclei out of the retina boundary; IGF-1, Ang II and VEGF expression levels of retinal tissue were detected by RT-PCR and Western blot.

A large area of non-perfusion and tortuous expansion form of the blood vessel was found in the optic nerve surroundings of retinal serial sections in model group, while neovascularization plexus and fluorescence leakage were observed between perfusion and non-perfusion area. Non-perfusion and neovascularization have experienced a decrease in IGF-1 overexpression group but an increase in IGF-1 siRNA group. The number of neovascularization endothelial nuclei out of the internal limiting membrane in model group was remarkably higher than that in control group. This number in IGF-1 over-expression group decreases while in IGF-1 siRNA group it increases, with a significant statistical difference (p < 0.05). Histone IGF-1 expression level in the model group was lower than that in the control group, but Ang II and VEGF expression level were higher. IGF-1 in over-expression group was higher but with a lower expression level of Ang II and VEGF; however, the results in siRNA group were opposite. The difference was statistically significant (p < 0.05).

The occurrence of retinal neovascularization is related to the reduction of IGF-1 expression and the increase of Ang II and VEGF.