Selective deletion of Slc2a1 from the RPE reveals that rods but not cones depend on glucose transport across the outer blood-retinal barrier

GLUT1 facilitates a continuous flow of glucose across the inner and outer blood-retinal barriers (BRBs) to support vision. To understand the extent to which photoreceptors rely on glucose transport across the outer BRB, we generated a tamoxifen-inducible conditional knockout of <i>Slc2a1</i> in the retinal pigment epithelium (RPE) (<i>RPE-iΔGlut1</i>). In the <i>RPE-iΔGlut1</i> mice, rod photoreceptors exhibited impaired outer segment renewal and decreased the expression of proteins involved in phototransduction and ciliary transport. Proteins regulating the retinal stress response increased. Cone photoreceptors were functional and viable 15 months post-tamoxifen treatment in the <i>RPE-iΔGlut1</i> mice, while 70% of the rods died. When <i>Slc2a1</i> was genetically deleted from rods (<i>Rod-iΔGlut1</i> mice), rod degeneration was faster than in the <i>RPE-iΔGlut1</i> mice. These findings suggest that rods are more dependent on glucose than cones, and that glucose from the deep vascular plexus may support cone function and viability and slow the rate of rod death.