Norrin在氧诱导的视网膜病变中的时空表达及其意义

目的：探讨视网膜新生血管疾病动物模型-氧诱导的视网膜病变（OIR）小鼠视网膜中Norrin的时空表达变化及意义。方法：荧光素灌注铺片观察OIR小鼠视网膜血管分布和形态。RT－PCR检测对照组P7、P10、P12、P17小鼠和OIR P7、P8、P12、P12.5、P13、P14、P15、P17、P19小鼠视网膜中Norrin、VEGF mRNA的表达。免疫组化法检测Norrin蛋白在视网膜中的表达和分布位置。结果：OIR小鼠P12时在视网膜后极部形成无灌注区，P17时有大量新生血管形成。Norrin mRNA在正常小鼠视网膜中表达水平低且稳定。缺氧12 h后，Norrin mRNA有显著升高，缺氧1 d到达高峰，然后缓慢下降，其变化趋势与VEGF mRNA一致。Norrin蛋白在正常小鼠各时点免疫组化均未能检出，在OIR模型中P15见弱表达，P17-P19表达明显增强。主要分布在视网膜外层，以内外节层、外丛状层为主。结论：Norrin在mRNA和蛋白水平都在缺氧视网膜中明显升高，主要分布在视网膜外层。Norrin很可能参与新生血管的形成，并起着重要的调控作用。

The temporal and spatial Norrin expression and significance in oxygen induced retinopathy

AIM: To detect the expression and location of Norrin in mouse retina with oxygen-induced retinopathy (OIR). METHODS: Retinal neovascular angiogenesis of OIR mouse was observed by FITC-Dextran filled retinamounts. Norrin, VEGF mRNA expression was studied by RT-PCR in control mouse retina on postnatal days 7, 10, 12, 17 and in OIR mouse retina on postnatal days 7, 8, 12, 12.5, 13, 14, 15, 17 and 19. Norrin protein expression and location was observed by immunohistochemical methods. RESULTS: Retinal neovasculature was observed in OIR ischemic mouse on postnatal days 17. Norrin mRNA expression markedly increased in retina after hypoxia 12 hours, which was correlated with the upregulation of VEGF. The peak of increase in Norrin occurred at 24 hours, and levels then decreased slowly. Norrin was expressed in outer layers of retina of P15-17 OIR mice, and was not found in normal control mice retina. CONCLUSION: Increased levels of Norrin in OIR ischemic retina show temporal correlation with increased expression of VEGF. Increased Norrin locates in outer layers of retina. Norrin may play an important role in neovascular angiogenesis.