Immunohistochemical localisation of intravitreally injected bevacizumab at the posterior pole of the primate eye: implication for the treatment of retinal vein occlusion.
OBJECTIVE
To locate bevacizumab in the posterior pole within 1-14 days after intravitreal injection in the primate eye.


METHODS
Four Cynomolgus monkeys received an intravitreal injection of 1.25 mg of bevacizumab. The eyes were enucleated on days 1, 4, 7 and 14 for immunohistochemistry using donkey anti-human Cy3-IgG. Control eyes remained untreated.


RESULTS
In the optic nerve, immunoreactivity for bevacizumab was most prominent on day 1 after injection and diminished rapidly. In the blood vessels of the nerve fibre layer, the staining was intense in the walls and weak in the lumen from day 1 to 4, and was only localised in the lumen thereafter. In the macula, an accumulation of bevacizumab was observed 1 day after injection in the nerve fibre layer, the ganglion cell layer and in the photoreceptors at the level of the outer nuclear layer in the fovea centralis.


CONCLUSIONS
Bevacizumab penetrates quickly into the macula, the retinal veins and the optic nerve after intravitreal injection in the primate eye, and accumulates preferentially and specifically on the vessel walls and inside the photoreceptors localised in the fovea centralis 1 day after injection. Our finding supports the clinically observed rapid effect in the treatment of retinal vein occlusion and macular oedema.
Julien
S
S
Section of Experimental Vitreoretinal Surgery, Centre of Ophthalmology, Institute for Ophthalmic Research, Tuebingen, Germany. sylvie.julien@med.uni-tuebingen.de
Heiduschka
P
P
Hofmeister
S
S
Schraermeyer
U
U
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D008269:Macular Edema / Q000188:drug therapy*; D009900:Optic Nerve / Q000187:drug effects* / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D012170:Retinal Vein Occlusion / Q000188:drug therapy*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014822:Vitreous Body / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab