Liver-Specific but Not Retina-Specific Hepcidin Knockout Causes Retinal Iron Accumulation and Degeneration.

08:00 EDT 6th July 2019 | BioPortfolio

Summary of "Liver-Specific but Not Retina-Specific Hepcidin Knockout Causes Retinal Iron Accumulation and Degeneration."

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 the liver. We previously demonstrated that systemic 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, due to retinal iron influx that would normally be regulated by retina-produced Hepc. To address this question, retinas of liver-specific (LS) and retina-specific (RS) HepcKO mice were studied. LS-Hepc KO mice had elevated blood and 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 RS-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.


Journal Details

This article was published in the following journal.

Name: The American journal of pathology
ISSN: 1525-2191


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