title: 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.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors.forename: Alexey
authors.initials: A
authors.lastname: Obolensky
authors.forename: Eduard
authors.initials: E
authors.lastname: Berenshtein
authors.forename: Michal
authors.initials: M
authors.lastname: Lederman
authors.forename: Baruch
authors.initials: B
authors.lastname: Bulvik
authors.forename: Ruslana
authors.initials: R
authors.lastname: Alper-Pinus
authors.forename: Ruth
authors.initials: R
authors.lastname: Yaul
authors.forename: Efrat
authors.initials: E
authors.lastname: Deleon
authors.forename: Itay
authors.initials: I
authors.lastname: Chowers
authors.forename: Mordechai
authors.initials: M
authors.lastname: Chevion
authors.forename: Eyal
authors.initials: E
authors.lastname: Banin
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002614:Chelating Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects; D003676:Deferoxamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D004195:Disease Models, Animal; D004596:Electroretinography; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D002614:Chelating Agents; D009942:Organometallic Compounds; C086228:zinc-desferrioxamine; D007501:Iron; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517438:Pde6b protein, mouse; D003676:Deferoxamine