TOXICITY and RETINAL PENETRATION of INFLIXIMAB in PRIMATES

Abstract

Purpose: To evaluate the retinal penetration and toxicity of two doses of intravitreal infliximab in primates.Methods: Ten marmosets (Callithrix jacchus) were given intravitreal injection of 100 mu g or 400 mu g of infliximab, and balanced salt solution served as control. At baseline and after 24 hours (5 animals) and 7 days (the other 5), the eyes were examined by electroretinography. They were then killed (at 24 hours and 7 days) and assessed by light microscopy and transmission electron microscopy for toxicity and immunohistochemistry, using a biotinylated anti-human immunoglobulin G, to evaluate retinal penetration.Results: There was no difference over 50% of the electroretinography b-wave between baseline and the time points studied in all animals. Light and electron microscopy, and electroretinography analysis, showed no signs of toxicity in any of the animals. Strong presence of infliximab was observed in all retinal layers 7 days after intravitreal injection at both doses (100 and 400 mu g).Conclusion: Infliximab at doses of 100 and 400 mu g seemed to cause no damage to the retina 24 hours and 7 days after its intravitreal injection, and deeply penetrated all its layers, in primates. These results encourage future perspectives for the treatment of chronic inflammatory diseases of the retina in humans. RETINA 32: 606-612, 2012