Iron is essential for life, but excess
iron can be toxic. As a potent
free radical creator,
iron generates
hydroxyl radicals leading to significant oxidative stress. Since
iron is not excreted from the body, it accumulates with age in tissues, including the retina, predisposing to age-related oxidative insult. Both hereditary and acquired
retinal diseases are associated with increased
iron levels. For example,
retinal degenerations have been found in hereditary
iron overload disorders, like
aceruloplasminemia,
Friedreich's ataxia, and
pantothenate kinase-associated neurodegeneration. Similarly, mice with targeted mutation of the
iron exporter
ceruloplasmin and its homolog hephaestin showed age-related
retinal iron accumulation and
retinal degeneration with features resembling human
age-related macular degeneration (AMD). Post mortem AMD eyes have increased levels of
iron in retina compared to age-matched healthy donors.
Iron accumulation in AMD is likely to result, in part, from
inflammation,
hypoxia, and oxidative stress, all of which can cause
iron dysregulation. Fortunately, it has been demonstrated by in vitro and in vivo studies that
iron in the retinal pigment epithelium (RPE) and retina is chelatable.
Iron chelation protects photoreceptors and
retinal pigment epithelial cells (RPE) in a variety of mouse models. This has therapeutic potential for diminishing
iron-induced oxidative damage to prevent or treat AMD.