TY - JOUR
T1 - Zinc-desferrioxamine attenuates retinal degeneration in the rd10 mouse model of retinitis pigmentosa
AU - Obolensky, Alexey
AU - Berenshtein, Eduard
AU - Lederman, Michal
AU - Bulvik, Baruch
AU - Alper-Pinus, Ruslana
AU - Yaul, Ruth
AU - Deleon, Efrat
AU - Chowers, Itay
AU - Chevion, Mordechai
AU - Banin, Eyal
PY - 2011/10/15
Y1 - 2011/10/15
N2 - 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.
AB - 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.
KW - Free radicals
KW - Iron
KW - Metallo-complex
KW - Oxidative stress
KW - Retinal degeneration
UR - http://www.scopus.com/inward/record.url?scp=80052697210&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2011.07.014
DO - 10.1016/j.freeradbiomed.2011.07.014
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C2 - 21824515
AN - SCOPUS:80052697210
SN - 0891-5849
VL - 51
SP - 1482
EP - 1491
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 8
ER -