The effect of D-Timolol and L-Timolol on rat experimental choroidal neovascularization vivo and endothelial cells in vitro / 国际眼科杂志(Guoji Yanke Zazhi)

ABSTRACT

·AIM: Impairment of choroidal perfusion was found in AMD patients. We postulated that vasoactive agents,which can reduce choroidal blood flow resistance, might prevent the development of choroidal neovascularization (CNV). D-Timolol and L-Timolol are hypotensive agents used in cardiovascular and glaucoma therapy. Their effects on laser-induced experimental CNV rat model and human umbilical vein endothelial cells (HUVEC) were thus evaluated.·METHODS: Male Brown Norway rats were anesthetized to receive NdYAG laser to break the Bruch's membrane. D-Timolol and L-Timolol were given once daily through intraperitoneal injection after laser treatment for 4wk. Fluorescein angiography was performed on 2wk and 4wk. HUVEC were tested by proliferation assay and adhesion assay with D-Timolol and L-Timolol at different concentrations.· RESULTS: D-Timolol reduced the fluorescein leakage to 83% of the control group in laser-induced rat's CNV model at a dosage of 15mg/(kg·d). L-Timolol had no effect on CNV formation even at a higher dosage of 20mg/(kg·d). D-Timolol inhibited the endothelial cells proliferation significantly by 300mg/L. L-Timolol also significantly inhibited the cell proliferation at 1 000mg/L. But at a lower dose such as 300mg/L, no significant inhibitory effect was found. Both drugs showed no effect on cell adhesion function in cell culture experiments.· CONCLUSION: D-Timolol was found to prevent CNV development in laser-induced model in vivo and inhibit vascular endothelial cells proliferation in vitro. L-Timolol had no effect on cell proliferation at the same dose, and neither on rat CNV model. The results indicate these two isomers have different functions on rat's CNV prevention and on HUVEC cell proliferation.