Targeted disruption of the FGF2 gene does not prevent choroidal neovascularization in a murine model
Targeted disruption of the FGF2 gene does not prevent choroidal neovascularization in a murine model
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DOI：
10.1016/s0002-9440(10)65753-7
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发表时间：
1998-11-01
影响因子：
6
通讯作者：
Campochiaro, PA
中科院分区：
文献类型：
--
作者：
Tobe, T;Ortega, S;Campochiaro, PA
脉络膜新生血管（CNV）是年龄相关性黄斑变性患者严重视力丧失的主要原因。激光治疗对少数CNV患者有帮助，但由于对所涉及的分子信号了解不足，阻碍了新治疗方法的发展。有几条证据表明碱性成纤维细胞生长因子（FGF2）在刺激CNV中起作用，在本研究中，我们在新建立的小鼠激光诱导CNV模型中使用靶向破坏FGF2基因的小鼠来验证这一假设。氪激光光凝治疗C57BL/6J小鼠一周后，60例烧伤中有34例（57%）出现荧光素泄漏，16例中有13例（81%）出现CNV的组织病理学证据。在激光治疗时观察到气泡的10个烧伤中有9个（90%）检测到CMI。电镜显示脉络膜新生血管病变内有大管腔的开窗血管。激光诱导Bruch膜破裂两周后，fgf2缺陷小鼠的36例烧伤中有27例（75%）含有CNV，而野生型对照小鼠的30例中有26例（87%）含有CNV，差异无统计学意义。本研究表明，激光诱导Bruch膜破裂后CNV的发展不需要FGF2，为研究CNV的分子机制和抗血管生成治疗提供了新的模型。
Choroidal neovascularization (CNV) is the major cause of severe visual loss Ln patients with age-related macular degeneration. Laser treatment is helpful for a minority of patients with CNV, and development of new treatments is hampered by a poor understanding of the molecular signals involved. Several lines of evidence have suggested that basic fibroblast growth factor (FGF2) plays a role in stimulating CNV, In this study, we tested this hypothesis using mice with targeted disruption of the FGF2 gene in a newly developed murine model of laser-induced CNV, One week after krypton laser photocoagulation in C57BL/6J mice, 34 of 60 burns (57%) showed fluorescein leakage and 13 of 16 (81%) showed histopathological evidence of CNV, At 2 weeks, CMI was detected in 9 of 10 burns (90%) in which a bubble had been observed at the time of the laser treatment. Electron microscopy showed fenestrated vessels with large lumens within choroidal neovascular lesions. Two weeks after laser-induced rupture of Bruch's membrane, 27 of 36 burns (75%) contained CNV in FGF2-deficient mice compared with 26 of 30 (87%) in wild-type control mice, a difference that is not statistically significant. This study demonstrates that FGF2 is not required for the development of CNV after laser-induced rupture of Bruch's membrane and provides a new model to investigate molecular mechanisms and anti-angiogenic therapy in CNV.