Heiduschka Peter, Fietz Heike, Hofmeister Sabine, Schultheiss Sigrid, Mack Andreas F, Peters Swaantje, Ziemssen Focke, Niggemann Birgit, Julien Sylvie, Bartz-Schmidt Karl Ulrich, Schraermeyer Ulrich
Experimental Vitreoretinal Surgery, Germany.
Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2814-23. doi: 10.1167/iovs.06-1171.
The penetration of intravitreally injected bevacizumab in its commercial formulation (Avastin; Roche, Grenzach, Germany) through the retina was studied, to determine whether a full-length antibody would be able to penetrate the retina as easily as an antibody fragment.
Six cynomolgus monkeys (Macaca fascicularis) were used in this study. Two compositions of intravitreal injection into the right eyes were performed: one with commercial Avastin (group 1, four animals) and the other one with commercial Avastin labeled with 125I (group 2, one animal). The animals in group 1 were killed 1, 4, 7, or 14 days after the injection for subsequent histologic analysis of the eyes by immunohistochemistry, and the animal in group 2 was killed 7 days after injection for autoradiography and electron microscopy. Funduscopy was performed before the injection and at several time points thereafter. Moreover, blood samples were collected at different time points from the group-2 animal. The sixth animal remained untreated and served as the control.
No pathologic changes were obvious in the funduscopic images within the time of the experiment. Bevacizumab immunoreactivity was found in the choroid and the inner layers of the retina as early as 1 day after the injection and spread to the outer layers and the choroid within the following days, in particular to photoreceptors and blood vessels. Avastin labeled with 125I showed radioactivity in blood serum 1 day after the intravitreal injection and remained relatively stable until day 7.
The results clearly show that the bevacizumab molecule can penetrate the retina and is also transported into the retinal pigment epithelium, the choroid and, in particular, into photoreceptor outer segments after intravitreal injection of Avastin. Active transport mechanisms seem to be involved.
研究玻璃体内注射商业制剂（阿瓦斯汀；罗氏公司，德国格伦扎赫）的贝伐单抗透过视网膜的情况，以确定全长抗体是否能像抗体片段一样容易地穿透视网膜。
本研究使用了6只食蟹猴（食蟹猕猴）。对右眼进行了两种玻璃体内注射制剂：一种是使用商业阿瓦斯汀（第1组，4只动物），另一种是使用用125I标记的商业阿瓦斯汀（第2组，1只动物）。第1组动物在注射后1、4、7或14天处死，随后通过免疫组织化学对眼睛进行组织学分析，第2组动物在注射后7天处死，用于放射自显影和电子显微镜检查。在注射前及之后的几个时间点进行眼底镜检查。此外，在不同时间点从第2组动物采集血样。第6只动物未接受治疗，作为对照。
在实验期间，眼底镜图像中未发现明显的病理变化。注射后1天，在脉络膜和视网膜内层发现贝伐单抗免疫反应性，在随后几天扩散到外层和脉络膜，特别是光感受器和血管。用125I标记的阿瓦斯汀在玻璃体内注射后1天在血清中显示放射性，并在第7天之前保持相对稳定。
结果清楚地表明，玻璃体内注射阿瓦斯汀后，贝伐单抗分子可穿透视网膜，并被转运至视网膜色素上皮、脉络膜，尤其是光感受器外段。似乎涉及主动转运机制。
