氧诱导视网膜病变中 netrin-1 的过度表达与血视网膜屏障的破坏和视网膜新生血管形成有关。
Netrin-1 overexpression in oxygen-induced retinopathy correlates with breakdown of the blood-retina barrier and retinal neovascularization.
机构信息
Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.
出版信息
Ophthalmologica. 2011;226(2):37-44. doi: 10.1159/000324474. Epub 2011 Apr 21.
PURPOSES
Recent research has shown netrin-1 to promote neovascularization. We evaluate the expression of netrin-1 during retinal neovascularization in a murine model of oxygen-induced retinopathy.
METHODS
C57BL/6J mice were exposed to 75 ± 5% oxygen for 5 days and returned to room air to induce retinal neovascularization. Retinal neovascularization was observed by fluorescence angiography and was quantified by counting the endothelial nuclei protruding into the vitreous cavity after hematoxylin-eosin staining. RT-PCR and Western blot analyses were used to determine retinal netrin-1 mRNA and protein levels at postnatal days (PN) 13, 15 and 17.
RESULTS
In fluorescence angiograms, irregular neovascularization and fluorescein leakage were observed surrounding the unperfused areas in the hypoxic group. The hypoxic group had, on average, 50.70 ± 4.56 neovascular nuclei protruding into the vitreous body, while similar nuclei were absent in the control group. Compared to the normoxic group, there were significant increases in both retinal netrin-1 mRNA and protein levels in the hypoxic group at PN13, PN15 and PN17.
CONCLUSION
The netrin-1 level increases in murine retina under hypoxia and may be key in inducing retinal neovascularization.
目的
最近的研究表明，轴突导向因子 1（netrin-1）可促进血管新生。我们在氧诱导的视网膜病变小鼠模型中评估了 netrin-1 在视网膜新生血管形成过程中的表达。
方法
C57BL/6J 小鼠暴露于 75±5%的氧气中 5 天，然后返回室内空气以诱导视网膜新生血管形成。通过荧光血管造影观察视网膜新生血管形成，并通过苏木精-伊红染色后计算突入玻璃体腔的内皮细胞核数进行定量。在出生后第 13、15 和 17 天，通过 RT-PCR 和 Western blot 分析来确定视网膜 netrin-1 mRNA 和蛋白水平。
结果
在荧光血管造影中，在缺氧组未灌注区域周围观察到不规则的新生血管和荧光素渗漏。缺氧组平均有 50.70±4.56 个新生血管核突入玻璃体，而对照组则没有类似的核。与正常氧组相比，在缺氧组的 PN13、PN15 和 PN17 时，视网膜 netrin-1 mRNA 和蛋白水平均显著升高。
结论
在低氧条件下，鼠视网膜中的 netrin-1 水平增加，可能是诱导视网膜新生血管形成的关键因素。
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