Inhibitory effect of small interfering RNA targeting peroxisome-proliferator-activated receptor-γ coactivator-1α on retinal neovascularization in the monse / 中华眼底病杂志

ABSTRACT

Objective To evaluate the inhibitory effect of small interfering RNA (siRNA) targeting peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α) on retinal neovascularization in the mouse.Methods Eighty seven-day-old C57BL/6J mice were divided into normal group,model blank group,model control group and PGC-1α siRNA group,twenty mice in each group.Mice in the normal group were kept in normal room air.Mice in the model blank group,model control group and PGC-1α siRNA group were induced for retinal neovascularization by hypoxia.Liposome with PGC-1α siRNA (1 μl) and liposome with negative control siRNA (1 μl) were injected into the vitreous in the PGC-1α siRNA group and model control group respectively when mice were moved out to room air from the cabin (Postnatal 12).No injection were performed in the model blank group.At postnatal 17,fluorescein angiography was used to assess the vascular pattern.The proliferative neovascular response was quantified by counting the nuclei of new vessels extending from the retina into the vitreous in cross-sections.PGC-1α and vascular endothelial growth factor (VEGF) level in retina were measured by real-time polymerase chain reaction (real-time PCR) and Western blot.Inhibition efficiency of PGC-1α siRNA on PGC-1α and VEGF was calculated.Results Mice in the normal group showed reticular distribution of retinal blood vessels.Central nonperfused retina,neovascular tufts and fluorescein leakage were seen in the model blank group and model control group.Neovascular tuft and fluorescein leakage were decreased in the PGC-1α siRNA group compared to the model blank group and model control group.The neovascular nuclei were increased in the model blank group and model control group compared to the normal group (P＜0.05).The neovascular nuclei were decreased in the PGC-1α siRNA group compared to the model blank group and model control group (P＜0.05).The expression of PGC-1α mRNA and protein in retina was increased significantly in the model blank group and model control group as compared with normal group,while decreased 54％ and 53％ respectively in the PGC-1α siRNA group as compared with model blank group and model control group (P＜0.05).The expression of VEGF mRNA and protein in retina was increased significantly in the model blank group and model control group as compared with normal group,while decreased significantly in the PGC-1α siRNA group (decreased 48 ％ and 40 ％ respectively) as compared with model blank group and model control group (P＜0.05).Conclusions Intravitreal injection of PGC-1α siRNA mediated by liposome can inhibit retinal neovascularization in the mouse effectively.