POLYMER CONJUGATION REDUCES DEFEROXAMINE INDUCED RETINOPATHY IN AN ALBINO-RAT MODEL

Purpose. The iron chelating agent deferoxamine mesylate USP (Desferal, Ciba, Summit, NJ) is commonly used in the treatment of acute iron int oxication and chronic iron overload (associated with the transfusion-d ependent anemias). When used for prolonged periods of time or in high doses deferoxamine is attended by a range of ocular toxicities. The vi sual symptoms associated with deferoxamine administration often limit effective iron chelation therapy and can result in permanent vision lo ss. Deferoxamine has recently been conjugated to certain high molecula r weight biocompatible polymers without altering its iron-binding prop erties. Here the effect of conjugation of deferoxamine to hydroxyethyl starch on retinal toxicity is examined. Methods. An albino rat model of electroretinographically determined, deferoxamine-induced retinal t oxicity has been previously described. We use this model to evaluate a nd compare both native deferoxamine and hydroxyethyl starch conjugated deferoxamine. Results. Our data show that retinal function, as assess ed by the electroretinogram b-wave, is significantly depressed 1 day a fter a single dose of native deferoxamine, while the b-waves of rats r eceiving a single dose of hydroxyethyl starch-deferoxamine, are not si gnificantly depressed at any time during the study. In addition, the a dministered dose of hydroxyethyl starch-deferoxamine resulted in plasm a deferoxamine concentrations up to five times greater than those achi eved with native deferoxamine. Conclusion. These results suggest that hydroxyethyl starch conjugated deferoxamine is associated with less re tinal toxicity than native deferoxamine and that it may be a safer alt ernative for iron chelation therapy.