Ocular safety of infliximab in rabbit and cell culture models

J Ocul Pharmacol Ther. 2010 Feb;26(1):65-71. doi: 10.1089/jop.2009.0035.

Abstract

Purpose: To undertake the safety testing of infliximab in animal and cell culture models.

Methods: Sixteen New Zealand albino rabbits were divided into 4 groups of 4 animals. Each group received 2 mg of infliximab in the right eye and saline solution in the left eye. Clinical examination and retinal histology were performed at months 1, 2, and 3 for groups A, B, and C, respectively. Electroretinography (ERG) recordings were made before the injection, and at months 1 and 2 for group D. The assessment of the safety of infliximab in retinal pigment epithelial (RPE) and retinal ganglion (RGC-5) cells was performed by Western blot analysis of caspase-3 involved in apoptosis pathway, the analysis of cytotoxicity of infliximab by WST-1 proliferation assay, and time-lapse video-microscopy to register the morphology of treated cells in time-lapse.

Results: Clinical examination of the eyes, histological study of the retina, and ERG recordings showed no sign of ocular toxicity after a single intravitreal injection of 2 mg of infliximab in the rabbit model. RPE and RGC viability was not reduced either in the range of concentration (up to 3 mg) or during the follow-up interval.

Conclusion: This study suggests that infliximab has no direct retinal toxicity using rabbit (2 mg) and cell culture (2 and 3 mg) models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / toxicity*
  • Antibodies, Monoclonal / toxicity*
  • Apoptosis / drug effects
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cell Line
  • Cell Proliferation / drug effects
  • Electroretinography
  • Humans
  • Infliximab
  • Rabbits
  • Retina / drug effects*
  • Retina / physiology
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / metabolism
  • Toxicity Tests / methods

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Infliximab
  • Caspase 3