Agostini Hansjürgen, Boden Karl, Unsöld Anke, Martin Gottfried, Hansen Lutz, Fiedler Ulrike, Esser Norbert, Marmé Dieter
Department of Ophthalmology, University of Freiburg, Freiburg Germany.
Curr Eye Res. 2005 Apr;30(4):249-57. doi: 10.1080/02713680590923249.
The purpose of this study was to develop pharmacological therapeutic alternatives for ischemia-induced proliferative retinopathy.
C57BL/6J mice were placed in 76% oxygen on postnatal day 7 (P7) for 5 days. On P12 recombinant, chimeric vascular endothelial growth factor (sVEGF-R2) or sTie2 was injected intravitreally in one eye. The fellow eye received a control injection. On P17, retinal wholemounts were prepared after perfusion with fluorescein-dextran to quantify the retinopathy.
A single intravitreal injection of sVEGF-R2 reduced pathologic vascular changes significantly (p = 0.02). No significant effect was observed after intravitreal application of sTie2 (p = 0.07), although Ang-2 was upregulated in control animals without treatment as neovascularization developed and Ang-1 was constantly transcribed (ratio PCR).
sVEGF-R2 interferes with VEGF signaling via VEGF-R2 receptor. Thus, local application of soluble receptors for angiogenic factors is a possible therapy for proliferative retinopathy. Receptors with a wide range of ligands might prove more useful for local application than those binding few or antagonistic ligands.
本研究旨在开发针对缺血性增殖性视网膜病变的药物治疗替代方案。
将C57BL/6J小鼠在出生后第7天（P7）置于76%氧气环境中5天。在P12时，将重组嵌合血管内皮生长因子（sVEGF-R2）或sTie2玻璃体内注射到一只眼睛中。另一只眼睛接受对照注射。在P17时，在用荧光素-葡聚糖灌注后制备视网膜全层标本以量化视网膜病变。
单次玻璃体内注射sVEGF-R2可显著减少病理性血管变化（p = 0.02）。玻璃体内应用sTie2后未观察到显著效果（p = 0.07），尽管在未治疗的对照动物中，随着新生血管形成，Ang-2上调而Ang-1持续转录（PCR比值）。
sVEGF-R2通过VEGF-R2受体干扰VEGF信号传导。因此，局部应用血管生成因子的可溶性受体是增殖性视网膜病变的一种可能治疗方法。与结合少数或拮抗配体的受体相比，具有广泛配体的受体可能在局部应用中更有用。
