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Penetration of Bevacizumab through the Retina after Intravitreal Injection in the Monkey
- Source :
- Investigative Opthalmology & Visual Science. 48:2814
- Publication Year :
- 2007
- Publisher :
- Association for Research in Vision and Ophthalmology (ARVO), 2007.
-
Abstract
- PURPOSE. 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. METHODS. 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 125 I (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. RESULTS. 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 125 I showed radioactivity in blood serum 1 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, into photoreceptor outer segments after intravitreal injection of Avastin. Active transport mechanisms seem to be involved.
- Subjects :
- Vascular Endothelial Growth Factor A
medicine.medical_specialty
genetic structures
Bevacizumab
Angiogenesis Inhibitors
Antibodies, Monoclonal, Humanized
Retina
Injections
Blood serum
Antibodies monoclonal
Ophthalmology
Photography
Animals
Medicine
Fluorescent Antibody Technique, Indirect
Pigment Epithelium of Eye
Retinal pigment epithelium
Choroid
business.industry
Antibodies, Monoclonal
Biological Transport
Anatomy
Penetration (firestop)
eye diseases
Vitreous Body
Macaca fascicularis
medicine.anatomical_structure
Autoradiography
Immunohistochemistry
sense organs
business
medicine.drug
Subjects
Details
- ISSN :
- 15525783
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Investigative Opthalmology & Visual Science
- Accession number :
- edsair.doi.dedup.....e7a73f7644825c2d8faadaf2fa798f99