bFGF诱导兔眼视网膜下新生血管形成的实验研究

Subretinal neovascularization induced by basic fibroblast growth factor in rabbit

目的探讨碱性成纤维细胞生长因子（bFGF）诱导青紫兰兔视网膜下新生血管动物模型的方法及可行性。方法健康成年青紫兰兔40只，随机分为2组。第1组实验组兔眼视网膜下注入0．005％（wt／vol）bFGF50μl，第2组对照组兔眼视网膜下注入0．9％生理盐水50μl，对侧眼均作为空白对照，不行视网膜下注射。术后3d，1、2、3、4、6、8、12周分别行眼底检查、摄片、眼底荧光血管造影（FFA）和吲哚青绿血管造影（ICGA），并行眼球组织病理学检查。结果视网膜下注射后所有眼即见视网膜直径4～5PD的青灰色半球形隆起，实验组与对照组分别于注射后2周和1周后平伏。术后2～12周FFA造影可见实验眼于视网膜隆起处下方早期斑点状高荧光，后期荧光增强并融合扩大。ICGA显示FFA高荧光相应部位荧光染料积存。对照组眼FFA、ICGA造影检查均未见类似表现。病理检查结果显示：视网膜下注射bFGF后2～12周，实验眼视网膜感光细胞层下有新生血管形成。结论视网膜下注入bFGF能成功诱导青紫兰兔视网膜下新生血管形成。

Objective Subretinal neovascularization （SRNV） is frequently occurred in macular diseases and is one of causes leading to blindness in population over 55 years. This study was to establish a new animal model of SRNV by subretinal injection of basic fibroblast growth factor（bFGF）. Methods Forty pigmented rabbits were divided into ：2 groups. SRNV was induced in ：24 rabbits by injection of 0. 005% （wt/vol） bFGF（ 50 μl,2.5 μg） into subretinal space of the right eye in experimental group,and the equal amount of physiological saline solution was injected at the same way in 16 rabbits of control group. Development of SRNV was observed for 1：2 weeks after surgery with ophthalmoscopy, fundus photography, fundus fluorescein angiography（FFA） and indocyanine green angiography（ICGA）. Eyes of rabbits were enucleated at different time points, and fundus lesions were evaluated for evidence of SRNV under the light microscopy. Results Fluorescein leakage and fluorescein deposit was observed by FFA and ICGA in the 2nd postoperative week and was more serious with following up until the lOth weeks,showing that SRNV was developed in all eyes in experimental group, however, no fluorescein leakage and fluorescein deposit were found in the eyes of control group. The dilation of choroidal vessel and neovascularization between the RPE and choroid were seen at the 4th week. Neovascularization,proliferated extra cellular matrix and migrated RPE on the upper layer of choroid could be seen,and subretinal fibrovascular membrane formed at the 6th week following establishment of model under the light microscope in the experimental eyes. No the discontinuation of Bruch＇ s membrane and new blood were seen in control eyes. Conclusion In pigmented rabbits, subretinal injection of bFGF leads to the development of SRNV, and these findings are similar to those of age-related macular degeneration. This model is useful for the study of the pathogenesis of SRNV and evaluation of potential treatment strategies.