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1From the Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania; 2The Whitney Laboratory of the University of Florida, St. Augustine, Florida; and the 3Department of Biochemistry, Nagoya University School of Medicine, Nagoya, Japan.
PURPOSE. The neural retina expresses multiple monocarboxylate transporters (MCTs) that are likely to play a key role in the metabolism of the outer retina. Recently, it was reported that targeting of MCT1 and -4 to the plasma membrane requires association with 5A11/basigin (CD147). In the present study, the hypothesis that reduced amplitudes in the electroretinograms in the 5A11/basigin null mouse (Bsg-/-) may be linked to altered expression of MCTs was studied.
METHODS. The expression and subcellular distribution of MCTs in Bsg-/- mice was analyzed by immunofluorescence microscopy with isoform-specific antibodies. Protein expression was analyzed by Western blot analysis, and mRNA expression was examined with RT-PCR.
RESULTS. Immunofluorescence labeling of tissue sections from the Bsg-/- mice revealed a dramatic reduction in labeling with MCT antibodies. There was a loss of MCT1 labeling in the apical membrane of the RPE and in the neural retina. MCT3, which is expressed in the basolateral membrane of the RPE wild-type mouse, was expressed at very low levels in both the apical and basolateral membranes of the Bsg-/- mouse. There was no change in expression or distribution of the glucose transporter (GLUT)-1 in the RPE and retina of the Bsg-/- mouse. Western blot analysis of detergent-soluble lysates prepared from wild-type and Bsg-/- eyes confirmed that the levels of MCT1, MCT3, and MCT4 protein were severely reduced in Bsg-/- mice. RT-PCR analyses of mRNA levels from wild-type and Bsg-/- mice demonstrated that the MCT1 transcript was expressed at normal levels in Bsg-/- mice.
CONCLUSIONS. In Bsg-/- mice, there is a severe reduction in accumulation of the MCT1 and -3 proteins in the RPE and a concomitant reduction in MCT1 and -4 in the neural retina supporting a role for 5A11/basigin in the targeting of these transporters to the plasma membrane. Decreased expression of MCT1 and -4 on the surfaces of Müller and photoreceptor cells may compromise energy metabolism in the outer retina, leading to abnormal photoreceptor cell function and degeneration.
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