title: Safety of intravitreal bevacizumab in the developing rabbit retina.
abstract: OBJECTIVE
  The purpose of this was to study the long-term effects of a single intravitreal dose of bevacizumab injected at different postnatal age on retinal function and development of retinal blood vessels in the adult albino rabbit.
  
  
  METHODS
  Bevacizumab was injected into the right eye of newborn rabbits, aged 11 days to 25 days, whereas the left eye of each rabbit was injected with identical volume of saline and served as control. The electroretinogram was recorded 1 week and 10 weeks after injection. Visual evoked potentials were recorded 10 weeks after injection. At termination of the follow-up period, the rabbits were killed and the retinas were prepared for histopathologic studies at the light microscopic level, for glial fibrillary acidic protein immunoreactivity, and for reduced form of nicotinamide adenine dinucleotide phosphate diaphorase histochemistry to assess the integrity of the retinal vascular system.
  
  
  RESULTS
  The electroretinogram responses demonstrated normal retinal function in adult rabbits injected at postnatal age of 11 days to 25 days. Mean Vmax and σ values calculated for each group of rabbits, 10 weeks after bevacizumab injection, indicated similar retinal function of the experimental and control eyes. Visual evoked potentials recorded by stimulating each eye separately were also similar. The histopathologic studies yielded similar results; no structural retinal damage was observed in the experimental eyes compared with the control eyes of rabbits from all age groups, and no increased glial fibrillary acidic protein immunoreactivity in Müller cells was observed in the experimental eyes. Staining of blood vessels with reduced form of nicotinamide adenine dinucleotide phosphate diaphorase revealed decreased branching of the capillary network in the experimental eyes compared with the control eyes in all age groups.
  
  
  CONCLUSIONS
  The electroretinographic and morphologic data showed no deleterious effects of a single intravitreal dose of bevacizumab, injected during the first 30 days postnatally, on the structural and functional integrity of the sensory retina in the adult rabbit. Even partial blockage of vascular endothelial growth factor with bevacizumab applied during retinal development seems to interfere with the development of the retinal vascular system in the albino rabbit. However, extrapolation from rabbits to humans should be made with caution.
authors.affiliation: Department of Ophthalmology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shiri
authors.initials: S
authors.lastname: Zayit-Soudry
authors.forename: Esther
authors.initials: E
authors.lastname: Zemel
authors.forename: Adiel
authors.initials: A
authors.lastname: Barak
authors.forename: Ido
authors.initials: I
authors.lastname: Perlman
authors.forename: Anat
authors.initials: A
authors.lastname: Loewenstein
mesh_terms: D020533:Angiogenesis Inhibitors / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D061067:Antibodies, Monoclonal, Humanized / Q000633:toxicity*; D000068258:Bevacizumab; D004596:Electroretinography / Q000187:drug effects*; D005074:Evoked Potentials, Visual / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D058449:Intravitreal Injections; D009252:NADPH Dehydrogenase / Q000378:metabolism; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D012171:Retinal Vessels / Q000254:growth & development / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D005904:Glial Fibrillary Acidic Protein; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D009252:NADPH Dehydrogenase