Polymer conjugation reduces deferoxamine induced retinopathy in an albino rat model.
OBJECTIVE
The iron chelating agent deferoxamine mesylate USP (Desferal, Ciba, Summit, NJ) is commonly used in the treatment of acute iron intoxication and chronic iron overload (associated with the transfusion-dependent anemias). When used for prolonged periods of time or in high doses deferoxamine is attended by a range of ocular toxicities. The visual symptoms associated with deferoxamine administration often limit effective iron chelation therapy and can result in permanent vision loss. Deferoxamine has recently been conjugated to certain high molecular weight biocompatible polymers without altering its iron-binding properties. 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 toxicity has been previously described. We use this model to evaluate and compare both native deferoxamine and hydroxyethyl starch conjugated deferoxamine.


RESULTS
Our data show that retinal function, as assessed by the electroretinogram b-wave, is significantly depressed 1 day after a single dose of native deferoxamine, while the b-waves of rats receiving a single dose of hydroxyethyl starch-deferoxamine, are not significantly depressed at any time during the study. In addition, the administered dose of hydroxyethyl starch-deferoxamine resulted in plasma deferoxamine concentrations up to five times greater than those achieved with native deferoxamine.


CONCLUSIONS
These results suggest that hydroxyethyl starch conjugated deferoxamine is associated with less retinal toxicity than native deferoxamine and that it may be a safer alternative for iron chelation therapy.
Gehlbach
P L
PL
Department of Physiology, University of Minnesota Medical School, Minneapolis 55455.
Purple
R L
RL
Hallaway
P E
PE
Hedlund
B E
BE
D000818:Animals; D003623:Dark Adaptation; D003676:Deferoxamine / Q000633:toxicity*; D004596:Electroretinography / Q000187:drug effects; D006895:Hydroxyethyl Starch Derivatives / Q000633:toxicity*; D008297:Male; D010775:Photic Stimulation; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects*; D012164:Retinal Diseases / Q000139:chemically induced
D006895:Hydroxyethyl Starch Derivatives; C068460:hydroxyethyl starch-deferoxamine conjugate; D003676:Deferoxamine