ArticleInvestigative ophthalmology & visual science2013
Loss of Hfe leads to progression of tumor phenotype in primary retinal pigment epithelial cells.
Article in Investigative ophthalmology & visual science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Redefining cell death: ferroptosis as a game-changer in ophthalmology.Frontiers in immunology · 2025Review
- Synaptotagmins family affect glucose transport in retinal pigment epithelial cells through their ubiquitination-mediated degradation and glucose transporter-1 regulation.World journal of diabetes · 2024Article
- Binding of Citrate-FeInternational journal of molecular sciences · 2022Article
- Does epigenetics have a role in age related macular degeneration and diabetic retinopathy?Genes & diseases · 2021Review
- Hereditary hemochromatosis promotes colitis and colon cancer and causes bacterial dysbiosis in mice.The Biochemical journal · 2020Article
- An Updated Review of the Epigenetic Mechanism Underlying the Pathogenesis of Age-related Macular Degeneration.Aging and disease · 2020Review
- [Progress on epigenetic regulation of iron homeostasis].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2020Review
- Chronic exposure to excess iron promotes EMT and cancer via p53 loss in pancreatic cancer.Asian journal of pharmaceutical sciences · 2020Article
- Extracellular Citrate Fuels Cancer Cell Metabolism and Growth.Frontiers in cell and developmental biology · 2020Review
- Article
- Iron Overload Accelerates the Progression of Diabetic Retinopathy in Association with Increased Retinal Renin Expression.Scientific reports · 2018Article
- Focusing on Sodium Glucose Cotransporter-2 and the Sympathetic Nervous System: Potential Impact in Diabetic Retinopathy.International journal of endocrinology · 2018Review
- Increased Retinal Expression of the Pro-Angiogenic Receptor GPR91 via BMP6 in a Mouse Model of Juvenile Hemochromatosis.Investigative ophthalmology & visual science · 2016Article
- Deletion of hemojuvelin, an iron-regulatory protein, in mice results in abnormal angiogenesis and vasculogenesis in retina along with reactive gliosis.Investigative ophthalmology & visual science · 2014Article
- Regulation of the cholesterol efflux transporters ABCA1 and ABCG1 in retina in hemochromatosis and by the endogenous siderophore 2,5-dihydroxybenzoic acid.Biochimica et biophysica acta · 2014Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
purposeHemochromatosis is a disorder of iron overload arising mostly from mutations in HFE. HFE is expressed in retinal pigment epithelium (RPE), and Hfe(-/-) mice develop age-related iron accumulation and retinal degeneration associated with RPE hyperproliferation. Here, the mechanism underlying the hyperproliferative phenotype in RPE was investigated.
methodsCellular senescence was monitored by β-galactosidase activity. Gene expression was monitored by real-time PCR. Survivin was analyzed by Western blot and immunofluorescence. Migration and invasion were monitored using appropriate kits. Glucose transporters (GLUTs) were monitored by 3-O-methyl-D-glucose uptake. Histone deacetylases (HDACs) were studied by monitoring catalytic activity and acetylation status of histones H3/H4.
resultsHfe(-/-) RPE cells exhibited slower senescence rate and higher survivin expression than wild type cells. Hfe(-/-) cells migrated faster and showed greater glucose uptake and increased expression of GLUTs. The expression of HDACs and DNA methyltransferase (DNMTs) also was increased. Similarly, RPE cells from hemojuvelin (Hjv)-knockout mice, another model of hemochromatosis, also had increased expression of GLUTs, HDACs, and DNMTs. The expression of Slc5a8 was decreased in Hfe(-/-) RPE cells, but treatment with a DNA methylation inhibitor restored the transporter expression, indicating involvement of DNA methylation in the silencing of Slc5a8 in Hfe(-/-) cells.
conclusionsRPE cells from iron-overloaded mice exhibit several features of tumor cells: decreased senescence, enhanced migration, increased glucose uptake, and elevated levels of HDACs and DNMTs. These features are seen in Hfe(-/-) RPE cells as well as in Hjv(-/-) RPE cells, providing a molecular basis for the hyperproliferative phenotype of Hfe(-/-) and Hjv(-/-) RPE cells.
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