Departmental Papers (Dental)
Document Type
Journal Article
Date of this Version
1-1-2019
Publication Source
American Journal of Physiology - Cell Physiology
Volume
316
Issue
1
Start Page
C121
Last Page
C133
Abstract
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 Glut1 flox/flox mice to generate Tg-Best1-Cre:Glut1 flox/flox mice (RPE∆Glut1). The RPE∆Glut1 mice displayed a mosaic pattern of Cre expression within the RPE that allowed us to analyze mice with ~50% (RPE∆Glut1 m ) recombination and mice with >70% (RPE∆Glut1 h ) 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. RPE∆Glut1 m 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. RPE∆Glut1 h mice showed outer segment shortening, cell death of photoreceptors, and activation of Müller glial cells. The severe phenotype seen in RPE∆Glut1 h 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. © 2019, American Physiological Society. All rights reserved.
Keywords
BEST1-cre; GLUT1; Müller glial cells; Photoreceptor cells; Retina
Recommended Citation
Swarup, A., Samuels, I. S., Bell, B. A., Han, J. Y., Du, J., Massenzio, E., Abel, E. D., Boesze-Battaglia, K., Peachey, N. S., & Philp, N. J. (2019). Modulating GLUT1 Expression in Retinal Pigment Epithelium Decreases Glucose Levels in the Retina: Impact on Photoreceptors and Müller Glial Cells. American Journal of Physiology - Cell Physiology, 316 (1), C121-C133. Retrieved from https://repository.upenn.edu/dental_papers/405
Date Posted: 08 December 2022
This document has been peer reviewed.