Modulating GLUT1 expression in retinal pigment epithelium decreases glucose levels in the retina: impact on photoreceptors and Müller glial cells
| العنوان: | Modulating GLUT1 expression in retinal pigment epithelium decreases glucose levels in the retina: impact on photoreceptors and Müller glial cells |
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| المؤلفون: | Jianhai Du, Brent A. Bell, Kathleen Boesze-Battaglia, E. Dale Abel, Erik Massenzio, Ivy S. Samuels, Nancy J. Philp, John Y. S. Han, Neal S. Peachey, Aditi Swarup |
| المصدر: | American Journal of Physiology-Cell Physiology. 316:C121-C133 |
| بيانات النشر: | American Physiological Society, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Physiology, Ependymoglial Cells, Gene Expression, Mice, Transgenic, Retinal Pigment Epithelium, Photoreceptor cell, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Photoreceptor Cells, Mice, Knockout, Glucose Transporter Type 1, Retina, Retinal pigment epithelium, biology, Chemistry, Cell Biology, eye diseases, Cell biology, Glucose, 030104 developmental biology, medicine.anatomical_structure, biology.protein, GLUT1, sense organs, 030217 neurology & neurosurgery, Research Article |
| الوصف: | The retina is one of the most metabolically active tissues in the body and utilizes glucose to produce energy and intermediates required for daily renewal of photoreceptor cell outer segments. Glucose transporter 1 (GLUT1) facilitates glucose transport across outer blood retinal barrier (BRB) formed by the retinal pigment epithelium (RPE) and the inner BRB formed by the endothelium. We used conditional knockout mice to study the impact of reducing glucose transport across the RPE on photoreceptor and Müller glial cells. Transgenic mice expressing Cre recombinase under control of the Bestrophin1 ( Best1) promoter were bred with Glut1flox/flox mice to generate Tg-Best1-Cre:Glut1flox/flox mice ( RPEΔGlut1). The RPEΔGlut1 mice displayed a mosaic pattern of Cre expression within the RPE that allowed us to analyze mice with ~50% ( RPEΔGlut1m) recombination and mice with >70% ( RPEΔGlut1h) recombination separately. Deletion of GLUT1 from the RPE did not affect its carrier or barrier functions, indicating that the RPE utilizes other substrates to support its metabolic needs thereby sparing glucose for the outer retina. RPEΔGlut1m mice had normal retinal morphology, function, and no cell death; however, where GLUT1 was absent from a span of RPE greater than 100 µm, there was shortening of the photoreceptor cell outer segments. RPEΔGlut1h mice showed outer segment shortening, cell death of photoreceptors, and activation of Müller glial cells. The severe phenotype seen in RPEΔGlut1h mice indicates that glucose transport via the GLUT1 transporter in the RPE is required to meet the anabolic and catabolic requirements of photoreceptors and maintain Müller glial cells in a quiescent state. |
| تدمد: | 1522-1563 0363-6143 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::992d9c5898fea71e2c9a7788156c074aTest https://doi.org/10.1152/ajpcell.00410.2018Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....992d9c5898fea71e2c9a7788156c074a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221563 03636143 |
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