Determination of Safety of Escalating Doses of Intravitreal Erythropoietin in Rabbit Eyes

To determine the maximum non-toxic dose of recombinant human erythropoietin (EPO) in rabbit eyes Eight rabbits (sixteen eyes) were scheduled for evaluating side effects of four intravitreal doses of 1000, 2000, 4000 and 5000 IU of EPO, two rabbits for each dose. For each dose (two rabbits), the drug was injected for the right eyes. Balanced salt solution (BSS) was injected into the left eye of one rabbit (placebo eye) and the other left eye remained uninjected (control eye). All eyes were examined in 1, 2, 3, 7, 14 and 28 days after intravitreal injections. Electroretinogarphy (ERG) was performed before and 14 days after intravitreal injection. After four weeks, animals were euthanized and eyes were enucleated and submitted for Hematoxylin & Eosin (H&E) and immunohistochemistry evaluations. Traumatic cataract developed in one of placebo group eyes. Neither anterior nor posterior segment inflammatory reactions were observed after injections. H&E staining and immunohistochemistry examinations did not revealed any sign of retinal and retinal pigment epithelium toxicity with injected doses. ERG changes were within normal limits in all eyes. Intravitreal injection of recombinant human EPO in rabbit eyes was not associated with adverse toxic effects up to 5000 IU doses.