| First Author | Swarup A | Year | 2019 |
| Journal | Am J Physiol Cell Physiol | Volume | 316 |
| Issue | 1 | Pages | C121-C133 |
| PubMed ID | 30462537 | Mgi Jnum | J:269598 |
| Mgi Id | MGI:6273693 | Doi | 10.1152/ajpcell.00410.2018 |
| Citation | Swarup A, et al. (2019) Modulating GLUT1 expression in retinal pigment epithelium decreases glucose levels in the retina: impact on photoreceptors and Muller glial cells. Am J Physiol Cell Physiol 316(1):C121-C133 |
| abstractText | 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 Muller glial cells. Transgenic mice expressing Cre recombinase under control of the Bestrophin1 ( Best1) promoter were bred with Glut1(flox/flox) mice to generate Tg-Best1-Cre:Glut1(flox/flox) mice ( RPEDeltaGlut1). The RPEDeltaGlut1 mice displayed a mosaic pattern of Cre expression within the RPE that allowed us to analyze mice with ~50% ( RPEDeltaGlut1m) recombination and mice with >70% ( RPEDeltaGlut1h) 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. RPEDeltaGlut1m mice had normal retinal morphology, function, and no cell death; however, where GLUT1 was absent from a span of RPE greater than 100 microm, there was shortening of the photoreceptor cell outer segments. RPEDeltaGlut1h mice showed outer segment shortening, cell death of photoreceptors, and activation of Muller glial cells. The severe phenotype seen in RPEDeltaGlut1h 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 Muller glial cells in a quiescent state. |
