Suppression of retinal neovascularization by small interfering RNA targeting PGC-1α
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.
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Document Type: Research Article
Affiliations: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Publication date: June 1, 2014
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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