Expression of glucose transporter‐2 in murine retina: Evidence for glucose transport from horizontal cells to photoreceptor synapses

The retina has the highest relative energy consumption of any tissue, depending on a steady supply of glucose from the bloodstream. Glucose uptake is mediated by specific transporters whose regulation and expression are critical for the pathogenesis of many diseases, including diabetes and diabetic retinopathy. Here, we used immunofluorescence to show that glucose transporter‐2 (GLUT2) is expressed in horizontal cells of the mouse neuroretina in proximity to inner retinal capillaries. To study the function of GLUT2 in the murine retina, we used organotypic retinal explants, cultivated under entirely controlled, serum‐free conditions and exposed them to streptozotocin, a cytotoxic drug transported exclusively by GLUT2. Contrary to our expectations, streptozotocin did not measurably affect horizontal cell viability, while it ablated rod and cone photoreceptors in a concentration‐dependent manner. Staining for poly‐ADP‐ribose (PAR) indicated that the detrimental effect of streptozotocin on photoreceptors may be associated with DNA damage. The negative effect of streptozotocin on the viability of rod photoreceptors was counteracted by co‐administration of either the inhibitor of connexin‐formed hemi‐channels meclofenamic acid or the blocker of clathrin‐mediated endocytosis dynasore. Remarkably, cone photoreceptors were not protected from streptozotocin‐induced degeneration by neither of the two drugs. Overall, these data suggest the existence of a GLUT2‐dependent glucose transport shuttle, from horizontal cells into photoreceptor synapses. Moreover, our study points at different glucose uptake mechanisms in rod and cone photoreceptors. Our study shows that glucose transporter‐2 (GLUT2) is expressed in horizontal cells of the mouse neuroretina, in proximity to inner retinal capillaries. GLUT2 function in horizontal cells was investigated by exposing murine retina to streptozotocin, a cytotoxic drug transported exclusively by GLUT2. Unexpectedly, streptozotocin did not reduce horizontal cell viability, but ablated rod and cone photoreceptors. The negative effect of streptozotocin on rod, but not on cone, viability was counteracted by inhibiting either hemi‐channels or endocytosis. These data suggest a GLUT2‐dependent glucose transport from horizontal cells to photoreceptors, with possible differences in glucose uptake mechanisms between rod and cone photoreceptors.