REP-1 depletion causes altered mitochondrial energy metabolism in CHM disease, shifting from glycolysis to lipid oxidation

Glucose transporters mainly mediate the glucose supply and diffusion thorough the retinal vasculature, choroid/RPE and photoreceptor cells. While the physiological mechanisms behind glucose supply have been well studied and described, how glucose supply dysfunction contributes to the phenotype of retinal disease is poorly understood.

Now we provide evidence that retinal energetic failure dependent by glucose supply defect explains large part of the phenotype of Choroideremia (CHM), an X-linked chorioretinal dystrophy caused by mutations in the Rab escort protein-1 (REP-1) gene. By interrogating the effect of REP-1 depletion in CHM, we found that alteration of glucose transporters GLUT-4 and GLUT-1 in the RPE/retina cells contribute to the CHM phenotype.