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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice

¹F. M. Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, School of Medicine, University of Pennsylvania; and ²Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania

Submitted 26 February 2008 ; accepted in final form 2 June 2008

To meet the high-energy demands of photoreceptor cells, the outer retina metabolizes glucose through glycolytic and oxidative pathways, resulting in large-scale production of lactate and CO₂. Mct3, a proton-coupled monocarboxylate transporter, is critically positioned to facilitate transport of lactate and H⁺ out of the retina and could therefore play a role in pH and ion homeostasis of the outer retina. Mct3 is preferentially expressed in the basolateral membrane of the retinal pigment epithelium and forms a heteromeric complex with the accessory protein CD147. To examine the physiological role of Mct3 in the retina, we generated mice with a targeted deletion in Mct3 (slc16A8). The overall retinal histology of 4- to 36-wk-old Mct3^–/– mice appeared normal. In the absence of Mct3, expression of CD147 was lost from the basolateral but not apical RPE. The saturated a-wave amplitude (a_max) of the scotopic electroretinogram (ERG) was reduced by approximately twofold in Mct3^–/– mice relative to wild-type mice. A fourfold increase in lactate in the retina suggested a decrease in outer-retinal pH. In single-cell recordings from superfused retinal slices, saturating amplitudes of single rod photocurrents (J_max) were comparable indicating that Mct3^–/– mouse photoreceptor cells were inherently healthy. Based on these data, we hypothesize that disruption of Mct3 leads to a potentially reversible decrease in subretinal space pH, thereby reducing the magnitude of the light suppressible photoreceptor current.

monocarboxylate transporter 3; lactate transport; retinal pigment epithleium; pH regulation; photoreceptor; electroretinogram

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