Enhancement of retinal recovery by conjugated deferoxamine after ischemia-reperfusion.
OBJECTIVE
Although toxic to the retina in its native form, the iron chelator deferoxamine (DFO) shows no apparent retinal toxicity when bound to hydroxyethyl-starch (HES). Conjugation of DFO does not alter its iron binding properties. Once bound, iron is no longer active in the production of toxic oxygen intermediates. This investigation seeks to determine whether HES-conjugated DFO (HES-DFO) protects against ischemia-reperfusion injury in the retina.


METHODS
Retinal ischemia was induced in cats, pretreated with HES-DFO, using both the vascular ligation and the increased intraocular pressure models. Retinal recovery was monitored by electroretinography. Fundal fluorescein angiography was performed in treated and untreated animals after ischemia-reperfusion.


RESULTS
Our results indicate that pretreatment with an intravenous bolus of HES-DFO, significantly enhances recovery of the postischemic b-wave and decreases fluorescein leakage after ischemia-reperfusion.


CONCLUSIONS
HES-DFO improves recovery of the neural retina after ischemia-reperfusion. It also maintains the integrity of the blood-retinal barrier. The protective effect of HES-DFO on the blood-retinal barrier is consistent with its intravascular confinement. That HES-DFO results in protection of the neural retina underscores the importance of the blood-retinal barrier as a mediator of ischemia-reperfusion injury. HES-DFO may have a role in the early management of ischemic retinal disease both as an iron chelator and as a blood-retinal barrier protector.
Gehlbach
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Department of Physiology, University of Minnesota Medical School, Minneapolis 55455.
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D000818:Animals; D001813:Blood-Retinal Barrier / Q000187:drug effects; D002415:Cats; D003676:Deferoxamine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004596:Electroretinography; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage*; D007275:Injections, Intravenous; D011897:Random Allocation; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D012160:Retina / Q000187:drug effects* / Q000502:physiology; D012171:Retinal Vessels / Q000187:drug effects / Q000503:physiopathology
D006895:Hydroxyethyl Starch Derivatives; C068460:hydroxyethyl starch-deferoxamine conjugate; D003676:Deferoxamine