Yanagi Yasuo, Tamaki Yasuhiro, Obata Ryo, Muranaka Kimimasa, Homma Noriko, Matsuoka Hidehito, Mano Hidetoshi
Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan.
Invest Ophthalmol Vis Sci. 2002 Nov;43(11):3495-9.
Bucillamine is an antirheumatic drug with antiangiogenic properties that is currently used in clinical practice. Because bucillamine inhibits the production of VEGF, it is possible that this drug may inhibit choroidal neovascularization (CNV). Thus, the effect of bucillamine on the eyes of rats with experimental CNV was investigated in vivo by subconjunctival injection or oral intake.
CNV was induced in rat eyes by diode laser photocoagulation. The intensity of fluorescein leakage from the photocoagulated lesions was studied 7 and 14 days after photocoagulation. The areas of CNV lesions were measured histologically and studied immunohistochemically at days 4, 7, and 14. In addition, the concentration of the drug in ocular tissue and blood was measured by high-performance liquid chromatography-tandem mass spectrometry after the drug was delivered orally or subconjunctivally.
After subconjunctival injection, fluorescein leakage from the CNV lesions decreased significantly compared with the control eyes throughout the study period. Histologic and immunohistochemical analyses 4, 7, and 14 days after photocoagulation demonstrated that the average size of the CNV lesions was reduced in the bucillamine-treated eyes compared with the control eyes. Subconjunctival injection maximized the ocular drug concentration while minimizing the blood concentration of the drug compared with oral intake.
Subconjunctival injection of bucillamine significantly reduced the leakage and size of experimental CNV. These results suggest that bucillamine may be beneficial in treating CNV and that further studies can be considered to evaluate this possibility.
布西拉明是一种具有抗血管生成特性的抗风湿药物，目前用于临床实践。由于布西拉明可抑制血管内皮生长因子（VEGF）的产生，因此该药物有可能抑制脉络膜新生血管形成（CNV）。因此，通过结膜下注射或口服给药，在体内研究了布西拉明对实验性CNV大鼠眼睛的影响。
用二极管激光光凝诱导大鼠眼睛产生CNV。在光凝后7天和14天研究光凝损伤处荧光素渗漏的强度。在第4、7和14天对CNV损伤区域进行组织学测量并进行免疫组织化学研究。此外，在口服或结膜下给药后，通过高效液相色谱-串联质谱法测量眼组织和血液中的药物浓度。
在整个研究期间，结膜下注射后，与对照眼相比，CNV损伤处的荧光素渗漏显著减少。光凝后4、7和14天的组织学和免疫组织化学分析表明，与对照眼相比，布西拉明治疗组的CNV损伤平均大小减小。与口服给药相比，结膜下注射可使眼内药物浓度最大化，同时使药物的血液浓度最小化。
结膜下注射布西拉明可显著减少实验性CNV的渗漏和大小。这些结果表明，布西拉明可能对治疗CNV有益，可考虑进一步研究以评估这种可能性。
