Ocular safety of infliximab in rabbit and cell culture models.

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.