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Conditional Müller Cell Ablation Leads to Retinal Iron Accumulation

Baumann, B; Sterling, J; Song, Y; Song, D; Fruttiger, M; Gillies, M; Shen, W; (2017) Conditional Müller Cell Ablation Leads to Retinal Iron Accumulation. Investigative Ophthalmology & Visual Science , 58 (10) pp. 4223-4234. 10.1167/iovs.17-21743. Green open access

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Abstract

PURPOSE: Retinal iron accumulation is observed in a wide range of retinal degenerative diseases, including AMD. Previous work suggests that Müller glial cells may be important mediators of retinal iron transport, distribution, and regulation. A transgenic model of Müller cell loss recently demonstrated that primary Müller cell ablation leads to blood–retinal barrier leakage and photoreceptor degeneration, and it recapitulates clinical features observed in macular telangiectasia type 2 (MacTel2), a rare human disease that features Müller cell loss. We used this mouse model to determine the effect of Müller cell loss on retinal iron homeostasis. METHODS: Changes in total retinal iron levels after Müller cell ablation were measured using inductively coupled plasma mass spectrometry. Corresponding changes in the expression of iron flux and iron storage proteins were determined using quantitative PCR, Western analysis, and immunohistochemistry. RESULTS: Müller cell loss led to blood–retinal barrier breakdown and increased iron levels throughout the neurosensory retina. There were corresponding changes in mRNA and/or protein levels of ferritin, transferrin receptor, ferroportin, Zip8, and Zip14. There were also increased iron levels within the RPE of retinal sections from a patient with MacTel2 and both RPE and neurosensory retina of a patient with diabetic retinopathy, which, like MacTel2, causes retinal vascular leakage. CONCLUSION: This study shows that Müller cells and the blood–retinal barrier play pivotal roles in the regulation of retinal iron homeostasis. The retinal iron accumulation resulting from blood–retinal barrier dysfunction may contribute to retinal degeneration in this model and in diseases such as MacTel2 and diabetic retinopathy.

Type: Article
Title: Conditional Müller Cell Ablation Leads to Retinal Iron Accumulation
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1167/iovs.17-21743
Publisher version: http://dx.doi.org/10.1167/iovs.17-21743
Language: English
Additional information: Copyright 2017 The Authors. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0).
Keywords: retina, iron, Zip8, Zip14, ferroportin, Mu¨ller cells, blood–retinal barrier, AMD, macular telangectasia type 2, diabetic retinopathy
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology > Institute of Ophthalmology - Cell Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1573322
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