Iron homeostasis and eye disease

Abstract

Background: Iron is necessary for life, but excess iron can be toxic to tissues. Iron is thought to damage tissues primarily by generating oxygen free radicals through the Fenton reaction.

Methods: We present an overview of the evidence supporting iron's potential contribution to a broad range of eye disease using an anatomical approach.

Results: Iron can be visualized in the cornea as iron lines in the normal aging cornea as well as in diseases like keratoconus and pterygium. In the lens, we present the evidence for the role of oxidative damage in cataractogenesis. Also, we review the evidence that iron may play a role in the pathogenesis of the retinal disease age-related macular degeneration. Although currently there is no direct link between excess iron and development of optic neuropathies, ferrous iron's ability to form highly reactive oxygen species may play a role in optic nerve pathology. Lastly, we discuss recent advances in prevention and therapeutics for eye disease with antioxidants and iron chelators.

General significance: Iron homeostasis is important for ocular health.

Figure 1

A schematic drawing of the cross-section of the eye. Reprinted with permission from Purves' Neuroscience published by Sinauer Associates in 1997. See legend for figure captions[15]).

Figure 2

A schematic drawing of the cell layers within the retina. (A) Section of the retina showing the cell layers of the retina. (B) A diagram of the arrangement of the retinal cells. Reprinted with permission from Purves' Neuroscience published by Sinauer Associates in 1997 [15])

Figure 3

UV photographs of bilateral corneas with Hudson-Stahli lines in a healthy elderly man. Reprinted with permission from Every et al. “Ultraviolet Photography of the In Vivo Human Cornea Unmasks the Hudson-Stähli Line and Physiologic Vortex Patterns” published in IOVS in 2005 [54])

Figure 4

Slit lamp photograph of a normal and keratoconus eye in profile. Reprinted with permission from Lawless et al “Keratoconus: diagnosis and management” in Australian and New Zealand Journal of Ophthalmology by Blackwell Synergy in 1989[63]).

Figure 5

Blue filter photography of the cornea of trauma patient with secondary keratoconus and a Fleischer's ring. Round Fleischer's ring-like pigment is observed (arrow). Reprinted with permission from Hiratsuka et al. “Secondary Keratoconus with Corneal Epithelial Iron Ring Similar to Fleischer's Ring” in Japanese Journal of Ophthalmology by SpringerLink in 2000 [43].

Figure 6

Photograph of a pterygium in the right eye. Reprinted by permission from Macmillan Publishers Lts in Memarzadeh et al “Comparison of de-epithelialized amniotic membrane transplantation and conjunctival autograft after primary pterygium excision” in Eye 2006 [67]).

Figure 7

A photograph of a patient with Salzmann's nodular degeneration. The left eye of a patient with Salzmann's nodular degeneration shows three blueish-white nodules located within the cornea. Reprinted with permission from Germundsson et al. “Phototherapeutic keratectomy in Salzmann's nodular degeneration” in Acta Ophthalmology Scandinavia by Blackwell Synergy in 2004 [80].

Figure 8

A slit lamp photograph showing iron deposits beneath the anterior lens capsule and the anterior lens opacity in ocular siderosis. Reprinted with permission from Hope-Ross et al. “Ocular Siderosis” in Eye by Nature Publishing Group[88].

Figure 9

Light microscopy of hyperferritinaemia cataract syndrome lenses. (A) Light microscopic appearance of crystalline inclusions within the lens stroma showing dense staining with monoclonal anti-L-ferritin (×400). (B) The deposits were not stained with anti-H-ferritin (×400). (C) Appearance of inclusions at ×50 000 magnification showing square-shaped crystal morphology. The crystals were not associated with any cellular elements, but appeared to lie free within the stroma. Reprinted with permission from Mumford et al. “The lens in hereditary hyperferritiniaemia cataract syndrome contains crystallin deposits of L-ferritin” in Br. J. Ophthal. by BMJ Publishing Group Ltd. [92]

Figure 10

Photomicrographs of increased Perls'-positive iron in age-related macular degeneration (AMD)–affected retinas. (A) Healthy macula has no Perls-3,3′-diaminobenzidine (DAB) stain after bleaching (inset) (B) Geographic atrophic macula with severe photoreceptor loss, RPE atrophy, and sub-RPE deposits. Bruch's membrane and sub-RPE deposits (sub) are positive for iron (inset). (C) Exudative AMD retina demonstrating significant photoreceptor loss with RPE atrophy and thickened BR. The RPE contains iron detectable by the Perls Prussian blue stain without DAB enhancement (inset). Scale bars indicate 50 μm. Reprinted figure and legend with permission from Hahn et al. “Maculas Affected by Age-Related Macular Degeneration Contain Increased Chelatable Iron in the Retinal Pigment Epithelium and Bruch's Membrane” in Arch Ophthalmol © 2003, American Medical Association. All rights reserved. [104]).