Testing intravitreal toxicity of rapamycin in rabbit eyes

Abstract

Purpose: To evaluate retinal toxicity of varying doses of rapamycin when injected intravitreally in rabbits. Rapamycin is a potent immunosuppressive agent with significant antitumor and antiangiogenic properties, clinically approved for prevention of organ transplant rejection. Methods: Twelve New Zealand albino rabbits were divided into four groups. Four different doses of rapamycin were prepared in 0.1 ml: 20 μg, 50 μg, 200 μg, and 1000 μg. Each concentration was injected in one eye of three rabbits, and 0.1 ml volume of sterile BSS was injected into the contralateral eye of the three rabbits. Slit-lamp and fundoscopic examinations were performed and the animals were observed for 2 weeks for signs of infection, inflammation, and toxicity. A baseline ERG was performed before drug treatment and at day 14, after which the rabbits were euthanized. Histology of the enucleated eyes was studied to look for retinal toxicity. Results: ERG results showed some decrease in scotopic response; however this was not dose related. ERG results were normal at 20 μg. Histological results showed no retinal toxicity in all groups. Conclusion: Although ERG changes were identified at dosages between 50-1000 μg, the histology of all groups up to 1000 μg did not show any discernable abnormalities.