Low ceruloplasmin levels exacerbate retinal degeneration in a hereditary hemochromatosis model

In a previous report, a 39-year-old patient with high serum iron levels from hereditary hemochromatosis (HH) was diagnosed with a form of retinal degeneration called bull's eye maculopathy. This is atypical for patients with HH, so it was theorized that the low serum levels of ferroxidase ceruloplasmin (CP) of this patient coupled with the high iron levels led to the retinal degeneration. CP, by oxidizing iron from its ferrous to ferric form, helps prevent the oxidative damage caused by ferrous iron. To test this, a hepcidin knockout (KO) mouse model of HH was combined with Cp KO to test whether the combination would lead to more severe retinal degeneration. Monthly in vivo retinal images were acquired and, after 11 months, mice were euthanized for further analyses. Both heterozygous and homozygous Cp KO increased the rate and severity of retinal degeneration. These results demonstrate the protective role of CP, which is most likely owing to its ferroxidase activity. The findings suggest that CP levels may influence the severity of retinal degeneration, especially in individuals with high serum iron.

Automated summary

In this report, a 39-year-old patient with hereditary hemochromatosis (HH) and high serum iron levels was diagnosed with bull's eye maculopathy, a form of retinal degeneration. The low levels of ferroxidase ceruloplasmin (CP) in the patient and the high iron levels were hypothesized to be the cause of the retinal degeneration. A mouse model combining hepcidin knockout (KO) and Cp KO was used to study the role of CP in retinal degeneration, and it was found that Cp KO increased the severity of retinal degeneration. These findings suggest that CP levels may influence the severity of retinal degeneration, particularly in individuals with high serum iron levels.