Liver-Specific, but Not Retina-Specific, Hepcidin Knockout Causes Retinal Iron Accumulation and Degeneration
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F19%3A00522699" target="_blank" >RIV/68378050:_____/19:00522699 - isvavai.cz</a>
Result on the web
<a href="https://dx.doi.org/10.1016/j.ajpath.2019.0.5.022" target="_blank" >https://dx.doi.org/10.1016/j.ajpath.2019.0.5.022</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ajpath.2019.0.5.022" target="_blank" >10.1016/j.ajpath.2019.0.5.022</a>
Alternative languages
Result language
angličtina
Original language name
Liver-Specific, but Not Retina-Specific, Hepcidin Knockout Causes Retinal Iron Accumulation and Degeneration
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10603 - Genetics and heredity (medical genetics to be 3)
Result continuities
Project
<a href="/en/project/LO1419" target="_blank" >LO1419: Biomodels for Health - Center for model organisms</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
American Journal of Pathology
ISSN
0002-9440
e-ISSN
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Volume of the periodical
189
Issue of the periodical within the volume
9
Country of publishing house
US - UNITED STATES
Number of pages
17
Pages from-to
1814-1830
UT code for WoS article
000483455900012
EID of the result in the Scopus database
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