Ishida K, Yoshimura N, Mandai M, Honda Y
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Japan.
Invest Ophthalmol Vis Sci. 1999 Jun;40(7):1512-9.
To determine whether an angiogenic inhibitor, TNP- 470 (TNP), an analogue of fumagillin, inhibits choroidal neovascularization (CNV) induced by diode laser photocoagulation in a rat experimental model.
Fundus laser photocoagulation was performed on Brown Norway rats to induce CNV. In the treatment group, TNP was administered intraperitoneally at the time of laser photocoagulation and on day 7 (50 mg/kg at each time). The incidence of CNV formation was evaluated by fluorescein angiography. The retina was collected from the rats on days 1, 3, 7, and 14 after laser photocoagulation, and semiquantitative polymerase chain reaction (PCR) analyses for the expression of mRNA of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were carried out. Localization of bFGF mRNA was studied by in situ reverse transcription-PCR (RT-PCR). The numbers of positively labeled cells for bFGF mRNA were compared between the TNP treatment and control groups.
The incidence of CNV formation was 22.7% in the TNP-treated rats and that in the control rats was 61.4% (P < 0.001). The semiquantitative PCR analyses showed that bFGF mRNA was upregulated on days 3 and 7 in the control rats, but no significant changes were found in TNP-treated rats. There was no detectable difference in VEGF gene expression between the control and TNP-treated rats. bFGF mRNA was detected by in situ RT-PCR in the regenerated retinal pigment epithelial cells and cells of the outer and inner nuclear layers of the control rats. The number of positive cells for bFGF mRNA in the TNP treatment group was significantly smaller than that of the control group (P < 0.05) on days 3 and 14.
TNP- 470 treatment reduced the incidence of laser-induced CNV formation in this experimental model. The expression of bFGF associated with CNV formation was also significantly reduced by the TNP treatment.
在大鼠实验模型中，确定血管生成抑制剂TNP-470（TNP，烟曲霉素类似物）是否能抑制二极管激光光凝诱导的脉络膜新生血管（CNV）。
对挪威棕色大鼠进行眼底激光光凝以诱导CNV。在治疗组中，于激光光凝时及第7天腹腔注射TNP（每次50mg/kg）。通过荧光素血管造影评估CNV形成的发生率。在激光光凝后第1、3、7和14天从大鼠收集视网膜，进行碱性成纤维细胞生长因子（bFGF）和血管内皮生长因子（VEGF）mRNA表达的半定量聚合酶链反应（PCR）分析。通过原位逆转录-PCR（RT-PCR）研究bFGF mRNA的定位。比较TNP治疗组和对照组中bFGF mRNA阳性标记细胞的数量。
TNP治疗组大鼠CNV形成的发生率为22.7%，对照组为61.4%（P<0.001）。半定量PCR分析显示，对照组大鼠在第3天和第7天bFGF mRNA上调，但TNP治疗组大鼠未发现明显变化。对照组和TNP治疗组大鼠之间VEGF基因表达无明显差异。通过原位RT-PCR在对照组大鼠再生的视网膜色素上皮细胞以及外核层和内核层细胞中检测到bFGF mRNA。在第3天和第14天，TNP治疗组中bFGF mRNA阳性细胞的数量明显少于对照组（P<0.05）。
在该实验模型中，TNP-470治疗降低了激光诱导的CNV形成的发生率。TNP治疗还显著降低了与CNV形成相关的bFGF的表达。
