ArticleInvestigative ophthalmology & visual science2014
Monomethylfumarate induces γ-globin expression and fetal hemoglobin production in cultured human retinal pigment epithelial (RPE) and erythroid cells, and in intact retina.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 33 citations in OpenAlex.
- Human retinal organoids for modelling dry age-related macular degeneration and screening drugs.Genes & diseases · 2025Article
- Bach1 inhibitor HPP-D mediates γ-globin gene activation in sickle erythroid progenitors.Blood cells, molecules & diseases · 2024Article
- Hemoglobin Subunit Theta 1 Promotes Proliferation by Reducing Reactive Oxygen Species in Lung Adenocarcinoma.Cancers · 2023Article
- The BACH1 inhibitor ASP8731 inhibits inflammation and vaso-occlusion and induces fetal hemoglobin in sickle cell disease.Frontiers in medicine · 2023Article
- Review
- Isolation of Primary Mouse Retinal Pigmented Epithelium Cells.Journal of visualized experiments : JoVE · 2022Article
- Article
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- Pharmacologic inducers of the uric acid exporter ABCG2 as potential drugs for treatment of gouty arthritis.Asian journal of pharmaceutical sciences · 2020Review
- Data on the role of miR-144 in regulating fetal hemoglobin production in retinal pigmented epithelial cells.Data in brief · 2020Article
- MIR29B mediates epigenetic mechanisms of HBG gene activation.British journal of haematology · 2019Article
- Nrf2 activation in myeloid cells and endothelial cells differentially mitigates sickle cell disease pathology in mice.Blood advances · 2019Article
- MIR-144-mediated NRF2 gene silencing inhibits fetal hemoglobin expression in sickle cell disease.Experimental hematology · 2019Article
- Loss of NRF2 function exacerbates the pathophysiology of sickle cell disease in a transgenic mouse model.Blood · 2018Article
- Dimethyl fumarate increases fetal hemoglobin, provides heme detoxification, and corrects anemia in sickle cell disease.JCI insight · 2017Article
- Anti-Psoriatic Drug Monomethylfumarate Increases Nuclear Factor Erythroid 2-Related Factor 2 Levels and Induces Aquaporin-3 mRNA and Protein Expression.The Journal of pharmacology and experimental therapeutics · 2017Article
- NRF2 mediates γ-globin gene regulation and fetal hemoglobin induction in human erythroid progenitors.Haematologica · 2017Article
- Control of Oxidative Stress and Inflammation in Sickle Cell Disease with the Nrf2 Activator Dimethyl Fumarate.Antioxidants & redox signaling · 2017Article
- Oral Monomethyl Fumarate Therapy Ameliorates Retinopathy in a Humanized Mouse Model of Sickle Cell Disease.Antioxidants & redox signaling · 2016Article
- Therapeutic fetal-globin inducers reduce transcriptional repression in hemoglobinopathy erythroid progenitors through distinct mechanisms.Blood cells, molecules & diseases · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
purposeSickle retinopathy (SR) is a major cause of vision loss in sickle cell disease (SCD). There are no strategies to prevent SR and treatments are extremely limited. The present study evaluated (1) the retinal pigment epithelial (RPE) cell as a hemoglobin producer and novel cellular target for fetal hemoglobin (HbF) induction, and (2) monomethylfumarate (MMF) as an HbF-inducing therapy and abrogator of oxidative stress and inflammation in SCD retina.
methodsHuman globin gene expression was evaluated by RT-quantitative (q)PCR in the human RPE cell line ARPE-19 and in primary RPE cells isolated from Townes humanized SCD mice. γ-Globin promoter activity was monitored in KU812 stable dual luciferase reporter expressing cells treated with 0 to 1000 μM dimethylfumarate, MMF, or hydroxyurea (HU; positive control) by dual luciferase assay. Reverse transcriptase-qPCR, fluorescence-activated cell sorting (FACS), immunofluorescence, and Western blot techniques were used to evaluate γ-globin expression and HbF production in primary human erythroid progenitors, ARPE-19, and normal hemoglobin producing (HbAA) and homozygous β(s) mutation (HbSS) RPE that were treated similarly, and in MMF-injected (1000 μM) HbAA and HbSS retinas. Dihydroethidium labeling and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), IL-1β, and VEGF expression were also analyzed.
resultsRetinal pigment epithelial cells express globin genes and synthesize adult and fetal hemoglobin MMF stimulated γ-globin expression and HbF production in cultured RPE and erythroid cells, and in HbSS mouse retina where it also reduced oxidative stress and inflammation.
conclusionsThe production of hemoglobin by RPE suggests the potential involvement of this cell type in the etiology of SR. Monomethylfumarate influences multiple parameters consistent with improved retinal health in SCD and may therefore be of therapeutic potential in SR treatment.
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