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.