Abstract

SA.08.07

Co-localisation of Avastin and VEGF in the monkey retina after intravitreal injection of Avastin

Schraermeyer U.¹, Bartz-Schmidt K.-U.², Heiduschka P.^1
1University Eye Hospital, Tübingen, Experimental Vitreoretinal Surgery; ²University Eye Hospital, Tübingen, Ophthalmology I

Objective: The penetration of intravitreally injected bevacizumab in its commercial formulation (Avastin^®) through the retina had to be studied, since there was speculation that a full-length antibody might not be able to penetrate the retina as easily as an antibody fragment.
Methods: Six cynomolgus monkeys (Macaca fascicularis) were used in this study. Two runs of intravitreal injection into the right eyes were performed, one with commercial Avastin^® (group 1, four animals) and the other with commercial Avastin^® labelled with 125I (group 2, one animal). The group 1 animals were sacrificed 1, 4, 7 or 14 days after the injection for subsequent histological analysis of the eyes by immuno-histochemistry, and the group 2 animal was sacrificed 7 days after injection for autoradiography and electron microscopy. Funduscopy was performed before the injection and at several points afterwards. Moreover, blood samples were collected at a different point from the group 2 animal. The sixth animal remained untreated and served as a control.
Results: No pathological changes were obvious in the funduscopic images within the period of the experiment. Bevacuizumab immunoreactivity was already found in the choroid and the inner layers of the retina one day after the injection and spread to the outer layers and the choroid within the following days, in particular to photoreceptors and blood vessels. Using Avastin^® labelled with 125I, radioactivity could already be detected in blood serum one day after the intravitreal injection, and remained relatively stable until day 7.
Conclusions: 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, the photoreceptor outer segments after intravitreail injection of Avastin^®. Active transport mechanisms seem to be involved.

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