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Inhibitory effect of TNP-470 on experimental choroidal neovascularization in a rat model
K Ishida1, N Yoshimura, M Mandai
1Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Japan.
Purpose:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
TNP-470 significantly reduced choroidal neovascularization (CNV) in a rat model. This angiogenic inhibitor also decreased basic fibroblast growth factor (bFGF) expression, a key factor in CNV development.
Area of Science:
- Ophthalmology
- Angiogenesis Research
- Molecular Biology
Background:
- Choroidal neovascularization (CNV) is a major cause of vision loss.
- Diode laser photocoagulation in rats is a standard model for studying CNV.
- Angiogenic factors like bFGF play a critical role in CNV pathogenesis.
Purpose of the Study:
- To evaluate the efficacy of TNP-470, an angiogenic inhibitor, in preventing laser-induced CNV in rats.
- To investigate the effect of TNP-470 on the expression of bFGF and VEGF in the context of CNV.
Main Methods:
- CNV was induced in Brown Norway rats using diode laser photocoagulation.
- TNP-470 was administered intraperitoneally to the treatment group.
- CNV incidence was assessed via fluorescein angiography.
- mRNA expression of bFGF and VEGF was analyzed using semiquantitative PCR and in situ RT-PCR.
Main Results:
- TNP-470 treatment reduced CNV incidence from 61.4% in controls to 22.7% (P < 0.001).
- bFGF mRNA upregulation observed in control rats was significantly inhibited by TNP-470 treatment.
- No significant changes in VEGF gene expression were detected between groups.
- In situ RT-PCR confirmed reduced bFGF mRNA-positive cells in TNP-470 treated rats.
Conclusions:
- TNP-470 effectively inhibits laser-induced CNV in a rat experimental model.
- The therapeutic effect of TNP-470 is associated with reduced expression of bFGF.