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Paul Hahn; Ann H. Milam, PhD; Joshua L. Dunaief, MD, PhD

Arch Ophthalmol. 2003;121:1099-1105.

Objective  To investigate whether iron is involved in the pathogenesis of age-related macular degeneration (AMD).

Methods  Postmortem AMD-affected (nonexudative or exudative) and healthy maculas were studied using the 3,3'-diaminobenzidine–enhanced Perls Prussian blue stain. The Perls Prussian blue stain was quantified by computer-assisted analysis of digital images. To determine whether the iron was chelatable, sections treated with the iron chelator deferoxamine were compared with adjacent, nonchelated sections.

Results  Compared with healthy maculas, AMD-affected maculas had statistically significant increases in the total iron level. Some of this iron was chelatable. The iron was present in retinal pigment epithelium and Bruch's membrane in maculas from patients who had drusen only, geographic atrophy, and exudative AMD in pathologic areas and, occasionally, in relatively healthy areas.

Conclusions  Oxidative stress has been implicated in the pathogenesis of AMD by the Age-Related Eye Disease Study. Increased concentrations of iron, which generate highly reactive hydroxyl radicals via the Fenton reaction, may induce oxidative stress in the macula and lead to AMD. As the increased iron concentrations in AMD-affected eyes consist in part of a chelatable iron pool, treatment of patients who have AMD with iron chelators might be considered a potential therapy. While there are, as yet, no clinical data indicating that the treatment of patients who have AMD with iron chelators is beneficial, data presented herein indicate that further investigation of iron concentrations in postmortem tissues and the mechanisms of iron transport in the retina is warranted.

From the F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia. The authors have no relevant financial interest in this article.

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