Iron is a potent generator of oxidative damage whose levels increase with age, potentially exacerbating age-related diseases. Several lines of evidence suggest that
iron accumulation may be
a factor in
age-related macular degeneration (AMD). AMD retinas have more
iron within the photoreceptors, RPE, and drusen than do age-matched control retinas. Accelerated AMD-like
maculopathy develops in patients with
retinal iron overload from the
hereditary disease aceruloplasminemia. Mice with
retinal iron overload resulting from knockout of
ceruloplasmin and its homologue hephaestin exhibit
retinal degeneration with some features of AMD, including subretinal neovascularization, accumulation of RPE
lipofuscin and sub-RPE deposits, and RPE/photoreceptor death. Increased understanding of the mechanisms of
retinal iron homeostasis may help in the development of
therapies to prevent
iron overload. For example, herein it is shown that one regulator of systemic
iron homeostasis, HFE, is expressed in the RPE. Thus, patients with the common
disease hereditary hemochromatosis, which is often caused by an HFE mutation, may have
retinal iron overload predisposing to AMD. Preliminary data suggest that
iron chelation can reduce RPE
iron overload in mice and protect them from degeneration, suggesting that
iron-binding drugs may one day prove useful in reducing RPE oxidative stress and decreasing the risk of AMD progression.