Kim Jaeryung, Kim Tae Eun, Kim Ju-A, Yun Ji-Hyun, Sohn Seongsoo, Shim Sang Ryeol, Lee Sang Hoon, Kim Sang Jin
1 The Laboratory of Vascular Biology and Stem Cells, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST) , Daejeon, Republic of Korea.
J Ocul Pharmacol Ther. 2014 Dec;30(10):847-53. doi: 10.1089/jop.2014.0021.
The study investigated the effect of intravitreally administered tanibirumab, a fully human monoclonal antibody against vascular endothelial growth factor receptor 2, in a rat model of laser-induced choroidal neovascularization (CNV).
CNV was induced by laser photocoagulation on day 0 in the eyes of Brown Norway rats. Intravitreal injection of tanibirumab or phosphate-buffered saline (PBS) was done on day 0 (prevention arm) or day 7 (treatment arm). Seven days after injection, the eyes were enucleated and retinal pigment epithelium-choroid-sclera flat mounts were prepared. Areas of CNV were determined in the flat mounts using tetramethylrhodamine isothiocyanate Bandeiraea simplicifolia (BS) isolectin labeling and intravenously administered fluorescein isothiocyanate-dextran and quantified using an image analysis program.
In the prevention arm, the mean area of CNV measured by BS isolectin labeling was reduced by 28.2% and 53.9% in tanibirumab-treated eyes (20 and 60 μg, respectively) compared with PBS-treated control eyes on day 7 (P=0.038 and P<0.001, respectively). In the treatment arm, the mean area of CNV measured by BS isolectin labeling was reduced by 28.7% and 46.0% in tanibirumab-treated eyes (20 and 60 μg, respectively) compared with PBS-treated control eyes on day 14 (P=0.048 and P<0.001, respectively).
Intravitreally administered tanibirumab partially suppressed the formation of new CNV and partially regressed preformed laser-induced CNV in the rat model. Tanibirumab may be a feasible treatment for CNV associated with age-related macular degeneration or other causes.
本研究在激光诱导脉络膜新生血管（CNV）大鼠模型中，调查玻璃体内注射完全人源化抗血管内皮生长因子受体2单克隆抗体他尼珠单抗的效果。
在第0天对挪威棕色大鼠眼进行激光光凝诱导CNV。在第0天（预防组）或第7天（治疗组）玻璃体内注射他尼珠单抗或磷酸盐缓冲盐水（PBS）。注射7天后，摘除眼球并制备视网膜色素上皮-脉络膜-巩膜铺片。使用异硫氰酸四甲基罗丹明单叶豆（BS）凝集素标记和平静脉注射异硫氰酸荧光素-葡聚糖，在铺片中确定CNV面积，并使用图像分析程序进行量化。
在预防组中，与第7天PBS处理的对照眼相比，他尼珠单抗处理的眼（分别为20和60μg）通过BS凝集素标记测量的CNV平均面积减少了28.2%和53.9%（P分别为0.038和P<0.001）。在治疗组中，与第14天PBS处理的对照眼相比，他尼珠单抗处理的眼（分别为20和60μg）通过BS凝集素标记测量的CNV平均面积减少了28.7%和46.0%（P分别为0.048和P<0.001）。
玻璃体内注射他尼珠单抗可部分抑制大鼠模型中新生CNV的形成，并使预先形成的激光诱导CNV部分消退。他尼珠单抗可能是治疗与年龄相关性黄斑变性或其他原因相关的CNV的可行疗法。
