June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Retinal degeneration associated with high systemic iron in mice and man
Author Affiliations & Notes
  • Joshua L Dunaief
    FM Kirby Ctr/Ophthalmology, University of Pennsylvania, Philadelphia, PA
  • Delu Song
    FM Kirby Ctr/Ophthalmology, University of Pennsylvania, Philadelphia, PA
  • Yafeng Li
    FM Kirby Ctr/Ophthalmology, University of Pennsylvania, Philadelphia, PA
  • Jessica Ijams Wolfing Morgan
    Scheie Eye Institute, Ophthalmology, University of Pennsylvania, Philadelphia, PA
  • Footnotes
    Commercial Relationships Joshua Dunaief, None; Delu Song, None; Yafeng Li, None; Jessica Morgan, 8226236 (P), Canon, Inc (C), Canon, Inc (F), Optos, Plc (F), Optos, Plc (R)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4216. doi:
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      Joshua L Dunaief, Delu Song, Yafeng Li, Jessica Ijams Wolfing Morgan; Retinal degeneration associated with high systemic iron in mice and man. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4216.

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

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Purpose: Iron is essential for metabolism but toxic in excess. It is unclear whether high blood iron levels can affect the retina, but a recent case of subacute-onset AMD in a 44yo woman following IV iron administration suggests this may occur. To evaluate this possibility, we delivered IV iron to mice, assessed retinal iron levels, and tested for retinal degeneration.

Methods: Fundus photography and OCT imaging were performed on the patient. Wild-type C57BL/6J mice were given 12 intravenous iron injections weekly beginning at age 2mo. Progression of retinopathy was assessed using monthly Micron III fundus photography. At age 9 months, mice were sacrificed and retinas analyzed for morphology in thin plastic sections, for iron accumulation by Perls' histochemical stain, and for the iron-regulated protein ferritin by immunofluorescence.

Results: The 44 yo patient had received annual dilated eye exams, as she is a glaucoma suspect. One year following IV iron treatment for anemia, she then complained of delayed dark adaptation and was noted to have many small and intermediate drusen, with two large drusen in each macula (AREDS category III). OCT and fundus photography showed many sub-RPE drusen in both eyes. Her visual acuity was 20/20, with no atrophy or neovascularization.<br /> <br /> Mice treated with IV iron developed multiple small hypopigmented retinal lesions detected by Micron III fundus photography. Plastic sectioning revealed focal vacuolar degeneration of the RPE, sometimes accompanied by loss of overlying photoreceptor outer segments. Perls' stain showed iron deposits in the RPE and choroid. Ferritin immunofluorescence was consistent with the Perls' stain, showing increased label in the RPE and choroid.

Conclusions: A patient treated with intravenous iron was found to have developed multiple macular drusen 1 year later. Mice given intravenous iron accumulated iron in the RPE and choroid, and developed focal RPE degeneration. These results support ongoing studies on the association of iron with AMD pathogenesis and suggest that retinal evaluations would be of interest in patients who have high systemic iron levels or are undergoing iron supplementation therapy.


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