title: 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.
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Xia
mesh_terms: D000818:Animals; D002460:Cell Line; D051379:Mice; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism / Q000473:pathology; D015861:Retinal Neovascularization / Q000628:therapy*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D034741:RNA, Small Interfering; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A