Suppression of Retinal Neovascularization by Lentivirus-Mediated Netrin-1 Small Hairpin RNA
Autor: | Xiaobo Xia, Jiaolian Liu, Hui-Zhuo Xu, Yun-Zheng Le, Si-Qi Xiong |
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Rok vydání: | 2011 |
Předmět: |
animal structures
genetic structures Blotting Western Genetic Vectors Retinal Neovascularization Real-Time Polymerase Chain Reaction Small hairpin RNA Mice Cellular and Molecular Neuroscience Retinal neovascularization Netrin medicine Animals Nerve Growth Factors Fluorescein Angiography RNA Small Interfering Original Paper biology medicine.diagnostic_test Tumor Suppressor Proteins Lentivirus fungi Gene Transfer Techniques General Medicine Netrin-1 biology.organism_classification medicine.disease Fluorescein angiography Molecular biology eye diseases Sensory Systems Cell biology Mice Inbred C57BL Disease Models Animal Ophthalmology Nerve growth factor Real-time polymerase chain reaction sense organs Retinopathy |
Zdroj: | Ophthalmic Research. 47:163-169 |
ISSN: | 1423-0259 0030-3747 |
Popis: | Objectives: The function of netrin-1 in pathological angiogenesis and its role in retinal neovascularization were investigated in the retinas of oxygen-induced retinopathy (OIR) mice by inhibition of netrin-1. Methods: Expression of netrin-1 mRNA and protein in the retinas of OIR mice was analyzed by quantitative RT-PCR and immunoblotting. Inhibition of retinal neovascularization was achieved by lentivirus-mediated netrin-1 small hairpin RNA (shRNA) infection. Retinal neovascularization was examined by fluorescein angiography and quantification of preretinal neovascular nuclei in retinal sections. Results: Both mRNA and protein expression of netrin-1 were significantly upregulated in postnatal day 17 OIR mouse retinas. Treatment of OIR mice with specific lentivirus-mediated netrin-1 shRNA dramatically reduced neovascular outgrowth into the inner limiting membrane. Neovascular tufts and nonperfused areas were also reduced. Conclusions: High expression of netrin-1 was detected in the retina under ischemic conditions and played a significant role in pathological retinal angiogenesis. Therefore, netrin-1 represents a potential therapeutic target for diabetic retinopathy, retinopathy of prematurity and other ocular neovascular diseases. |
Databáze: | OpenAIRE |
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