Photoreceptors consume glucose supplied by the choriocapillaris to support phototransduction and outer segment (OS) renewal. Reduced glucose supply underlies photoreceptor cell death in inherited retinal degeneration and age-related retinal disease. We have previously shown that restricting glucose transport into the outer retina by conditional deletion of Slc2a1 encoding GLUT1 resulted in photoreceptor loss and impaired OS renewal. However, retinal neurons, glia, and the retinal pigment epithelium play specialized, synergistic roles in metabolite supply and exchange, and the cell-specific map of glucose uptake and utilization in the retina is incomplete. In these studies, we conditionally deleted Slc2a1 in a pan-retinal or rod-specific manner to better understand how glucose is utilized in the retina. Using non-invasive ocular imaging, electroretinography, and histochemical and biochemical analyses we show that genetic deletion of Slc2a1 from retinal neurons and Müller glia results in reduced OS growth and progressive rod but not cone photoreceptor cell death. Rhodopsin levels were severely decreased even at postnatal day 20 when OS length was relatively normal. Arrestin levels were not changed suggesting that glucose uptake is required to synthesize membrane glycoproteins. Rod-specific deletion of Slc2a1 resulted in similar changes in OS length and rod photoreceptor cell death. These studies demonstrate that glucose is an essential carbon source for rod photoreceptor cell OS maintenance and viability.
Daniele, Lauren L.; Han, John Y.S.; Samuels, Ivy S; Komirisetty, Ravikiran; Mehta, Nikhil; McCord, Jessica L; Yu, Minzhong; Wang, Yekai; Boesze-Battaglia, Kathleen; Bell, Brent A; Du, Jianhai; Peachey, Neal S; and Philp, Nancy J., "Glucose Uptake by GLUT1 in Photoreceptors is Essential for Outer Segment Renewal and rod Photoreceptor Survival" (2022). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 363.
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