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Zinc-desferrioxamine attenuates retinal degeneration in the rd10 mouse model of retinitis pigmentosa.
- Source :
-
Free radical biology & medicine [Free Radic Biol Med] 2011 Oct 15; Vol. 51 (8), pp. 1482-91. Date of Electronic Publication: 2011 Jul 23. - Publication Year :
- 2011
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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.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Biomarkers metabolism
Chelating Agents adverse effects
Chelating Agents chemistry
Cyclic Nucleotide Phosphodiesterases, Type 6 genetics
DNA Damage drug effects
Deferoxamine adverse effects
Deferoxamine chemistry
Disease Models, Animal
Electroretinography
Genetic Predisposition to Disease
Humans
Immunohistochemistry
Lipid Peroxidation drug effects
Mice
Mice, Mutant Strains
Organometallic Compounds adverse effects
Organometallic Compounds chemistry
Oxidative Stress drug effects
Retina metabolism
Retina pathology
Retinitis Pigmentosa pathology
Retinitis Pigmentosa physiopathology
Chelating Agents administration & dosage
Deferoxamine administration & dosage
Iron metabolism
Organometallic Compounds administration & dosage
Retina drug effects
Retinitis Pigmentosa drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4596
- Volume :
- 51
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Free radical biology & medicine
- Publication Type :
- Academic Journal
- Accession number :
- 21824515
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2011.07.014