Koh Hyoung J, Bessho Kenichiro, Cheng Lingyun, Bartsch Dirk-Uwe, Jones Terence R, Bergeron-Lynn Germain, Freeman William R
Joan and Irwin Jacobs Retina Center, Department of Ophthalmology, Shiley Eye Center, University of California, San Diego, La Jolla, California, USA.
Invest Ophthalmol Vis Sci. 2004 Feb;45(2):635-40. doi: 10.1167/iovs.03-0735.
To evaluate the inhibitory effects of a urokinase-derived octapeptide A6 on laser-induced choroidal neovascularization (CNV).
In the first arm of the study, subcutaneous injection of A6 (200 mg/kg per day) into the right eyes in 20 rats and phosphate-buffered saline in 20 control rats was started 1 day before laser injury. Angiography was performed at week 2. To evaluate the dose response, a second arm of the study was performed in the left eyes. Half of the treatment group was treated with 400 mg/kg per day, and the remaining half continued to receive 200 mg/kg per day beginning on week 4. Laser injury was made at week 5 and angiography was performed at week 7. Angiographic evaluation, histopathologic evaluation including maximum CNV thickness and factor-VIII-stained endothelium counting were performed in the second arm of the study. Choroidal concentrations of A6 were measured.
In the first arm of the study, angiography showed a 40.8% reduction in CNV in the 200-mg/kg per day treatment group, compared with the control (P = 0.0008). In the second arm of the study, angiographic reduction in CNV was 37.9% in the 200-mg/kg per day group (P = 0.0314) and 70.0% in the 400-mg/kg per day group (P = 0.0124), compared with the control. CNV was significantly less in the 400-mg/kg per day group than in the 200-mg/kg per day group (P = 0.0393). Both CNV thickness and number of endothelial cells were reduced in a dose-dependent manner and significantly less than in the control (P < 0.05). Mean choroidal concentration of A6 2 hours after injection was 0.72 micro M in the 200-mg/kg per day (100 mg/kg every 12 hours) and 1.75 micro M in the 400-mg/kg per day (200 mg/kg every 12 hours) treatment groups. Levels at 11 hours after injections were undetectable.
A6 demonstrated antiangiogenic properties in a rat model of CNV and may be useful in the treatment of CNV.
评估尿激酶衍生的八肽A6对激光诱导的脉络膜新生血管形成（CNV）的抑制作用。
在研究的第一组中，于激光损伤前1天开始对20只大鼠的右眼皮下注射A6（每天200mg/kg），对20只对照大鼠注射磷酸盐缓冲盐水。在第2周进行血管造影。为评估剂量反应，在左眼进行研究的第二组。治疗组的一半每天接受400mg/kg治疗，另一半从第4周开始继续接受每天200mg/kg的治疗。在第5周进行激光损伤，在第7周进行血管造影。在研究的第二组中进行血管造影评估、组织病理学评估，包括最大CNV厚度和因子VIII染色内皮细胞计数。测量脉络膜中A6的浓度。
在研究的第一组中，血管造影显示每天200mg/kg治疗组的CNV较对照组减少40.8%（P = 0.0008）。在研究的第二组中，与对照组相比，每天200mg/kg组的CNV血管造影减少率为37.9%（P = 0.0314），每天400mg/kg组为70.0%（P = 0.0124）。每天400mg/kg组的CNV明显少于每天200mg/kg组（P = 0.0393）。CNV厚度和内皮细胞数量均呈剂量依赖性降低，且明显少于对照组（P < 0.05）。每天200mg/kg（每12小时100mg/kg）治疗组注射后2小时A6的平均脉络膜浓度为0.72μM，每天400mg/kg（每12小时200mg/kg）治疗组为1.75μM。注射后11小时检测不到其水平。
A6在CNV大鼠模型中表现出抗血管生成特性，可能对CNV的治疗有用。
