Modulating GLUT1 expression in retinal pigment epithelium decreases glucose levels in the retina: impact on photoreceptors and Müller glial cells

• DOI: 10.1152/ajpcell.00410.2018
• Publication Date: 2018-11-21T17:56:45Z
• Authors: Aditi Swarup; Ivy S. Samuels; Brent A. Bell; John Y. S. Han; Jianhai Du; Erik Massenzio; E. Dale Abel; Kathleen Boesze-B...; Neal S. Peachey; Nancy J. Philp
• Keywords: Blood–retinal barrier

The retina is one of the most metabolically active tissues in body and utilizes glucose to produce energy intermediates required for daily renewal photoreceptor cell outer segments. Glucose transporter 1 (GLUT1) facilitates transport across blood retinal barrier (BRB) formed by pigment epithelium (RPE) inner BRB endothelium. We used conditional knockout mice study impact reducing RPE on Müller glial cells. Transgenic expressing Cre recombinase under control Bestrophin1 ( Best1) promoter were bred with Glut1flox/flox generate Tg-Best1-Cre:Glut1flox/flox RPEΔGlut1). RPEΔGlut1 displayed a mosaic pattern expression within that allowed us analyze ~50% RPEΔGlut1m) recombination >70% RPEΔGlut1h) separately. Deletion GLUT1 from did not affect its carrier or functions, indicating other substrates support metabolic needs thereby sparing retina. RPEΔGlut1m had normal morphology, function, no death; however, where was absent span greater than 100 µm, there shortening RPEΔGlut1h showed segment shortening, death photoreceptors, activation severe phenotype seen indicates via meet anabolic catabolic requirements photoreceptors maintain cells quiescent state.