The liver secretes
hepcidin (Hepc) into the bloodstream to reduce blood
iron levels. Hepc accomplishes this by triggering degradation of the only known cellular
iron exporter
ferroportin in the gut, macrophages, and liver. We previously demonstrated that systemic Hepc knockout (HepcKO) mice, which have high serum
iron, develop
retinal iron overload and degeneration. However, it was unclear whether this is caused by high blood
iron levels or, alternatively,
retinal iron influx that would normally be regulated by retina-produced Hepc. To address this question, retinas of liver-specific and retina-specific HepcKO mice were studied. Liver-specific HepcKO mice had elevated blood and retinal pigment epithelium (RPE)
iron levels and increased free (labile)
iron levels in the retina, despite an intact blood-retinal barrier. This led to RPE
hypertrophy associated with
lipofuscin-laden lysosome accumulation. Photoreceptors also degenerated focally. In contrast, there was no change in
retinal or RPE
iron levels or degeneration in the retina-specific HepcKO mice. These data indicate that high blood
iron levels can lead to retinal iron accumulation and degeneration. High blood
iron levels can occur in patients with hereditary
hemochromatosis or result from use of
iron supplements or multiple
blood transfusions. Our results suggest that high blood
iron levels may cause or exacerbate
retinal disease.