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

Free Radic Biol Med. 2011 Oct 15;51(8):1482-91. doi: 10.1016/j.freeradbiomed.2011.07.014. Epub 2011 Jul 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Chelating Agents / administration & dosage*
  • Chelating Agents / adverse effects
  • Chelating Agents / chemistry
  • Cyclic Nucleotide Phosphodiesterases, Type 6 / genetics
  • DNA Damage / drug effects
  • Deferoxamine / administration & dosage*
  • Deferoxamine / adverse effects
  • Deferoxamine / 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*
  • Organometallic Compounds / adverse effects
  • Organometallic Compounds / chemistry
  • Oxidative Stress / drug effects
  • Retina / drug effects*
  • Retina / metabolism
  • Retina / pathology
  • Retinitis Pigmentosa / drug therapy*
  • Retinitis Pigmentosa / pathology
  • Retinitis Pigmentosa / physiopathology

Substances

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