Effect of tetramethylpyrazine on rat experimental choroidal neovascularization in vivo and endothelial cell cultures in vitro.
OBJECTIVE
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 (<or= 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 micro g/ml, 100 micro g/ml, and 30 micro 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.
Zou
Yanhong
Y
Department of Neuroscience and Experimental Therapeutics, Institute of Ocular Pharmacology, College of Medicine, Texas A&M University System Health Science Center. College Station, Texas. USA.
Jiang
Wei
W
Chiou
George C Y
GC
D000818:Animals; D002199:Capillary Permeability; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000517:prevention & control*; D003911:Dextrans / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005451:Fluorescein Angiography; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D007274:Injections, Intraperitoneal; D017075:Laser Coagulation; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011914:Rats, Inbred BN; D014471:Umbilical Veins / Q000166:cytology
D003911:Dextrans; D010975:Platelet Aggregation Inhibitors; D011719:Pyrazines; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; C017953:tetramethylpyrazine