Intravitreal tanibirumab, a fully human monoclonal antibody against vascular endothelial growth factor receptor 2, partially suppresses and regresses laser-induced choroidal neovascularization in a rat model

J Ocul Pharmacol Ther. 2014 Dec;30(10):847-53. doi: 10.1089/jop.2014.0021.

Abstract

Purpose: The study investigated the effect of intravitreally administered tanibirumab, a fully human monoclonal antibody against vascular endothelial growth factor receptor 2, in a rat model of laser-induced choroidal neovascularization (CNV).

Methods: CNV was induced by laser photocoagulation on day 0 in the eyes of Brown Norway rats. Intravitreal injection of tanibirumab or phosphate-buffered saline (PBS) was done on day 0 (prevention arm) or day 7 (treatment arm). Seven days after injection, the eyes were enucleated and retinal pigment epithelium-choroid-sclera flat mounts were prepared. Areas of CNV were determined in the flat mounts using tetramethylrhodamine isothiocyanate Bandeiraea simplicifolia (BS) isolectin labeling and intravenously administered fluorescein isothiocyanate-dextran and quantified using an image analysis program.

Results: In the prevention arm, the mean area of CNV measured by BS isolectin labeling was reduced by 28.2% and 53.9% in tanibirumab-treated eyes (20 and 60 μg, respectively) compared with PBS-treated control eyes on day 7 (P=0.038 and P<0.001, respectively). In the treatment arm, the mean area of CNV measured by BS isolectin labeling was reduced by 28.7% and 46.0% in tanibirumab-treated eyes (20 and 60 μg, respectively) compared with PBS-treated control eyes on day 14 (P=0.048 and P<0.001, respectively).

Conclusions: Intravitreally administered tanibirumab partially suppressed the formation of new CNV and partially regressed preformed laser-induced CNV in the rat model. Tanibirumab may be a feasible treatment for CNV associated with age-related macular degeneration or other causes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / etiology
  • Choroidal Neovascularization / pathology
  • Disease Models, Animal
  • Humans
  • Intravitreal Injections
  • Laser Coagulation
  • Plant Lectins / chemistry
  • Random Allocation
  • Rats
  • Staining and Labeling / methods
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Griffonia simplicifolia lectins
  • Plant Lectins
  • Vascular Endothelial Growth Factor Receptor-2
  • olinvacimab