Quantification and Localization of the IGF/Insulin System Expression in Retinal Blood Vessels and Neurons during Oxygen-Induced Retinopathy in Mice
Quantification and Localization of the IGF/Insulin System Expression in Retinal Blood Vessels and Neurons during Oxygen-Induced Retinopathy in Mice
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DOI：
10.1167/iovs.08-2903
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发表时间：
2009-04-01
影响因子：
4.4
通讯作者：
Smith, Lois E. H.
中科院分区：
文献类型：
--
作者：
Lofqvist, Chatarina;Willett, Keirnan L.;Smith, Lois E. H.
目的。视网膜病变是胰岛素样生长因子(IGF)-1影响病理性血管生成的结果。方法：采用实时荧光定量RT-PCR法，检测了IGF-1受体(IGF-1R)、胰岛素受体(IR)、IGF-1、IGF-2、胰岛素(Ins2)和IGF结合蛋白1(IGFBP1)到IGFBP6在整个视网膜中的表达，以检测视网膜病变和激光捕获视网膜成分中IGFBP6随时间的变化，以定量地定位于神经节细胞层、外核层、内核层和P33天结果：IGF-1R和IR主要在光感受器和血管中表达，在其余神经视网膜中很少表达。IGF-1R的表达是IR的100多倍。主要的局部生长因子(在光感受器和血管中表达)是IGF-2(大约是IGF-1的1000倍)。IGF-1(约600个拷贝/106个亲环素)表达于整个视网膜。IGFBP2、IGFBP4和IGfbp5的表达随着视网膜发育的增加和视网膜病变的诱发而变化不大。相反，IGFBP3的表达在缺氧时增加了5倍以上，在新生血管中发现。结论：IGF-1R、IR和配体IGF-2几乎仅在光感受器和血管中表达。与正常血管相比，新生血管中IGFBP3和Igfbp5的表达增加。IGF-1在整个视网膜中的表达水平要低得多。这些结果表明，血管和光感受器之间在视网膜病变和视网膜血管系统的发展中存在串扰。《投资眼科》2009年；50：1831年-1837年)DOI：10.1167
PURPOSE. Retinopathy is a result of pathologic angiogenesis influenced by insulinlike growth factor (IGF)-1. The authors examined the local expression of the IGF/insulin family.METHODS. In retinas with and without oxygen-induced retinopathy, the authors assessed with real-time RT-PCR mRNA expression of the IGF-1 receptor (IGF-1R), insulin receptor (IR), IGF-1, IGF-2, insulin (Ins2), and IGF-binding protein 1 (IGFBP1) to IGFBP6 in total retina from postnatal day (P) 7 to P33 to examine changes over time with the induction of retinopathy and at P17 on laser-captured retinal components to quantitatively localize mRNA expression in the ganglion cell layer, the outer nuclear layer, the inner nuclear layer, normal blood vessels, and neovascular tufts.RESULTS. IGF-1R and IR are expressed predominantly in photo-receptors and in vessels, with scant expression in the rest of the neural retina. IGF-1R expression is more than 100-fold greater than IR. The major local growth factor (expressed in photoreceptors and in blood vessels) is IGF-2 (approximately 1000-fold greater than IGF-1). IGF-1 (approximately 600 copies/106 cyclophilin) is expressed throughout the retina. IGFBP2, IGFBP4, and IGFBP5 expression is unchanged with increasing retinal development and with the induction of retinopathy. In contrast, IGFBP3 expression increased more than 5-fold with hypoxia, found in neovascular tufts.CONCLUSIONS. IGF-1R, IR, and the ligand IGF-2 are expressed almost exclusively in photoreceptors and blood vessels. IGFBP3 and IGFBP5 expression increases in neovascular tufts compared with normal vessels. IGF-1 is expressed throughout the retina at much lower levels. These results suggest cross-talk between vessels and photoreceptors in the development of retinopathy and retinal vasculature. (Invest Ophthalmol Vis Sci.2009;50:1831-1837) DOI:10.1167/iovs.08-2903