Effect of Tetramethylpyrazine on Rat Experimental Choroidal Neovascularization In Vivo and Endothelial Cell Cultures In Vitro

Abstract

Purpose: To evaluate the effect of tetramethylpyrazine (TMP) on laser-induced experimental choroidal neovascularization (CNV) in rat model in vivo and on endothelial cell proliferation in vitro. Methods: Male Brown Norway rats were anesthetized to receive Nd:YAG laser to break the Bruch membrane. TMP was given once daily through intraperitoneal injection after laser treatment for 4 weeks. The development of CNV was determined by angiography performed on week 2 and week 4 using sodium fluorescein (FA) or fluorescein isothiocyanate-dextran (FD70-FA). Human umbilical vein endothelial cells (HUVECs) were tested with proliferation assay with TMP at different concentrations. Results: According to the angiograms of FA, intensity of fluorescein leakage from the photocoagulated lesions decreased significantly after TMP treatment. The number of rats with less leaky points (≤ 75%) increased significantly in the TMP 40 mg/kg group (p < 0.05). The angiograms of FD70-FA showed diminished lesion size in the TMP-treated group. Four weeks after laser, the size of the CNV lesion was 2.69 ± 0.24 mm² in the control group, 2.00 ± 0.14 mm² in the TMP 20 mg/kg group, and 1.77 ± 0.10 mm² (p < 0.05) in the TMP 40 mg/kg group, respectively. TMP also interfered with endothelial cell proliferation significantly. The reduction of the endothelial cells was 53.7% (p < 0.05), 35.8% (p < 0.05), and 22.9% (p < 0.01), respectively, in the 300 μ g/ml, 100 μ g/ml, and 30 μ g/ml TMP-treated groups. Conclusions: TMP inhibited the development of CNV in the rat model and interfered with vascular endothelial cell proliferation in vitro. TMP may be useful in the treatment of CNV.

KEYWORDS:

• Choroidal neovascularization
• endothelial cell
• tetramethylpyrazine