慢病毒介导的轴突导向因子 netrin-1 短发夹 RNA 抑制视网膜新生血管。
Suppression of retinal neovascularization by lentivirus-mediated netrin-1 small hairpin RNA.
机构信息
Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.
出版信息
Ophthalmic Res. 2012;47(3):163-9. doi: 10.1159/000331428. Epub 2011 Nov 26.
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.
目的
通过抑制 netrin-1 来研究 netrin-1 在病理性血管生成中的作用及其在视网膜新生血管形成中的作用。
方法
通过定量 RT-PCR 和免疫印迹分析 OIR 小鼠视网膜中 netrin-1 mRNA 和蛋白的表达。通过慢病毒介导的 netrin-1 短发夹 RNA (shRNA) 感染抑制视网膜新生血管形成。通过荧光血管造影和视网膜切片中视网膜前新生血管核的定量来检测视网膜新生血管形成。
结果
在出生后第 17 天的 OIR 小鼠视网膜中，netrin-1 的 mRNA 和蛋白表达均显著上调。用特异性慢病毒介导的 netrin-1 shRNA 处理 OIR 小鼠可显著减少内界膜内的新生血管生长。新生血管丛和无灌注区也减少。
结论
在缺血条件下检测到 netrin-1 在视网膜中高表达，并在病理性视网膜血管生成中发挥重要作用。因此，netrin-1 是糖尿病性视网膜病变、早产儿视网膜病变和其他眼部新生血管疾病的潜在治疗靶点。
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