May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Iron Overloaded Cp–/–Heph–/– Retinas Exhibit Increased Light Damage and Thinning of Outer Nuclear Layer
Author Affiliations & Notes
  • Y. Qian
    Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA
  • T. Dentchev
    Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA
  • P. Krajacic
    Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA
  • P. Hahn
    Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA
  • J.L. Dunaief
    Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA
  • Footnotes
    Commercial Relationships  Y. Qian, None; T. Dentchev, None; P. Krajacic, None; P. Hahn, None; J.L. Dunaief, None.
  • Footnotes
    Support  NIH EY00417, RPB, IRRF, The Steinbach Foundation, RO1 EY 015240
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 1647. doi:
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      Y. Qian, T. Dentchev, P. Krajacic, P. Hahn, J.L. Dunaief; Iron Overloaded Cp–/–Heph–/– Retinas Exhibit Increased Light Damage and Thinning of Outer Nuclear Layer . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1647.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Ceruloplasmin (Cp) and its homolog hephaestin (Heph) are ferroxidases that facilitate iron export from cells. They are thought to reduce oxidative stress by maintaining iron homeostasis. Patients with aceruloplasminemia have retinal degeneration and elevated retinal iron levels. Since light causes photo–oxidative stress, it seems plausible that bright or prolonged light exposure might exacerbate retinal degeneration in an iron overloaded retina. To test this hypothesis, we exposed Cp and Heph double knockout (DKO) mice, which have retinal iron overload, to continuous bright light. Conversely, iron chelation with the drug deferoxamine (DFO) might ameliorate retinal degeneration, and we are also testing this hypothesis. Methods: Cp/Heph DKO and control mice, all 5 months old, were exposed for 10 days to constant cool white fluorescent light. Mice were euthanized 10 days after light damage and eyes were prepared for plastic and cryo sectioning. In the DFO experiment five month old DKO and control mice received intraperitoneal injection of DFO for 7 weeks, then eyes were prepared for plastic and paraffin sectioning, with Perls' staining for iron to test whether DFO could reduce iron levels and thereby protect against age–dependent retinal degeneration in the DKO mice. Results: Continuous light exposure caused significant thinning of the outer nuclear layer and RPE death in DKO but not control mice. The DFO exposed mice are currently being tested for retinal iron levels by the Perls' histochemical stain. Conclusions: These preliminary data suggest the importance of the protective effect of Cp and Heph in light damage, presumably by reducing oxidative stress. Since retinal iron accumulation is age dependent in DKOs, additional experiments with light damage in younger DKOs will test whether the increased susceptibility to light damage in DKOs is due to loss of Cp and Heph or to iron overload. DFO results will determine whether iron chelation can reduce RPE iron levels and protect the retina from degeneration.

Keywords: cell death/apoptosis • retinal degenerations: cell biology • oxidation/oxidative or free radical damage 
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