Suppression of retinal neovascularization by small interfering RNA targeting PGC-1α

Abstract

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a key coordinator of gene programs in metabolism and energy homeostasis in mammals. The aim of this study was to determine whether PGC-1α is involved in the transcriptional regulation of retinal neovascularization in oxygen-induced retinopathy (OIR). The expression of PGC-1α in the retina of mice with OIR was detected by real-time polymerase chain reaction (PCR) and western blot analysis. Mice with OIR were administered small interfering RNA (siRNA) targeting PGC-1α by intravitreal injection, and the effects of PGC-1α siRNA were confirmed by fluorescein angiography and quantification of pre-retinal neovascular nuclei in the retinal sections. PGC-1α was upregulated at both the mRNA and protein level under hypoxic conditions. Retinal neovascularization was inhibited by PGC-1α siRNA. Furthermore, PGC-1α mRNA and protein levels were also reduced by PGC-1α siRNA, which were detected by real-time PCR and western blot analysis. The downregulation of PGC-1α expression resulted in the reduction of vascular endothelial growth factor (VEGF) expression in the mice. In conclusion, siRNA targeting PGC-1α inhibits retinal neovascularization by downregulating the expression of PGC-1α and VEGF in the murine retina. Therefore, PGC-1α represents a potential therapeutic target for ischemia-induced retinal diseases and other ocular neovascular diseases.