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Suppression of retinal neovascularization by small interfering RNA targeting PGC-1α.
Suppression of retinal neovascularization by small interfering RNA targeting PGC-1α.
- Source :
-
International journal of molecular medicine [Int J Mol Med] 2014 Jun; Vol. 33 (6), pp. 1523-30. Date of Electronic Publication: 2014 Mar 31. - Publication Year :
- 2014
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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.
- Subjects :
- Animals
Cell Line
Mice
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
RNA, Small Interfering genetics
Real-Time Polymerase Chain Reaction
Retina metabolism
Retina pathology
Transcription Factors genetics
Vascular Endothelial Growth Factor A genetics
Vascular Endothelial Growth Factor A metabolism
RNA, Small Interfering pharmacology
Retinal Neovascularization therapy
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1791-244X
- Volume :
- 33
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- International journal of molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 24682380
- Full Text :
- https://doi.org/10.3892/ijmm.2014.1717