Zinc-desferrioxamine attenuates retinal degeneration in the rd10 mouse model of retinitis pigmentosa.

Abstract

Iron-associated oxidative injury plays a role in retinal degeneration such as age-related macular degeneration and retinitis pigmentosa. The metallo-complex zinc-desferrioxamine (Zn/DFO) may ameliorate such injury by chelation of labile iron in combination with release of zinc. We explored whether Zn/DFO can affect the course of retinal degeneration in the rd10 mouse model of retinitis pigmentosa. Zn/DFO-treated animals showed significantly higher electroretinographic responses at 3 and 4.5 weeks of age compared with saline-injected controls. Corresponding retinal (photoreceptor) structural rescue was observed by quantitative histological and immunohistochemical techniques. When administered alone, the components of the complex, Zn and DFO, showed a lesser, partial effect. TBARS, a marker of lipid peroxidation, and levels of oxidative DNA damage as quantified by 8-OHdG immunostaining were significantly lower in Zn/DFO-treated retinas compared with saline-injected controls. Reduced levels of retinal ferritin as well as reduced iron content within ferritin molecules were measured in Zn/DFO-treated retinas. The data, taken together, suggest that the protective effects of the Zn/DFO complex are mediated through modulation of iron bioavailability, leading to attenuation of oxidative injury. Reducing iron-associated oxidative stress using complexes such as Zn/DFO may serve as a "common pathway" therapeutic approach to attenuate injury in retinal degeneration.

• Authors: Alexey Obolensky, Eduard Berenshtein, Michal Lederman, Baruch Bulvik, Ruslana Alper-Pinus, Ruth Yaul, Efrat Deleon, Itay Chowers, Mordechai Chevion, Eyal Banin
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 51 Issue 8 Pg. 1482-91 (Oct 15 2011) ISSN: 1873-4596 [Electronic] United States
• PMID: 21824515 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Chelating Agents
• Organometallic Compounds
• zinc-desferrioxamine
• Iron
• Cyclic Nucleotide Phosphodiesterases, Type 6
• Pde6b protein, mouse
• Deferoxamine

Topics

• Animals
• Biomarkers (metabolism)
• Chelating Agents (administration & dosage, adverse effects, chemistry)
• Cyclic Nucleotide Phosphodiesterases, Type 6 (genetics)
• DNA Damage (drug effects)
• Deferoxamine (administration & dosage, adverse effects, chemistry)
• Disease Models, Animal
• Electroretinography
• Genetic Predisposition to Disease
• Humans
• Immunohistochemistry
• Iron (metabolism)
• Lipid Peroxidation (drug effects)
• Mice
• Mice, Mutant Strains
• Organometallic Compounds (administration & dosage, adverse effects, chemistry)
• Oxidative Stress (drug effects)
• Retina (drug effects, metabolism, pathology)
• Retinitis Pigmentosa (drug therapy, pathology, physiopathology)