Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 51, Issue 8, Pages 1482-1491Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2011.07.014
Keywords
Retinal degeneration; Iron; Oxidative stress; Metallo-complex; Free radicals
Funding
- Yedidut Research Grant
- Israel Science Foundation (ISF) [316/05]
- Israeli Ministry of Health
- Dr. Abraham Moshe and Paula Pepka Bergman Memorial Fund
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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. (C) 2011 Elsevier Inc. All rights reserved.
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